bims-bac4me Biomed News
on Microbiome and trained immunity
Issue of 2024‒04‒21
thirty-six papers selected by
Chun-Chi Chang, University Hospital Zurich
  1. The potency of hematopoietic stem cell reprogramming for changing immune tone.
  2. Soluble Human Lectins at the Host-Microbe Interface.
  3. Innate immunity-With an adaptive twist.
  4. A modified BCG with depletion of enzymes associated with peptidoglycan amidation induces enhanced protection against tuberculosis in mice.
  5. Exploring the lung microbiome's role in disease.
  6. A Robust In Vitro Culture Model and Generation of Memory Monocytes.
  7. Application of Microbiome-Based Therapies in Chronic Respiratory Diseases.
  8. Airway injury induces alveolar epithelial and mesenchymal responses mediated by macrophages.
  9. Bacterial surface lipoproteins mediate epithelial microinvasion by Streptococcus pneumoniae.
  10. Strategies of bacterial detection by inflammasomes.
  11. Dihydroartemisinin is an inhibitor of trained immunity through Akt/mTOR/HIF1α signaling pathway.
  12. Human genetic associations of the airway microbiome in chronic obstructive pulmonary disease.
  13. Bacteria deploy umbrella toxins against their competitors.
  14. Single-cell transcriptional landscape of temporal neutrophil response to burn wound in larval zebrafish.
  15. Current progresses and challenges for microbiome research in human health: a perspective.
  16. Squalene-epoxidase-catalyzed 24(S),25-epoxycholesterol synthesis promotes trained-immunity-mediated antitumor activity.
  17. Pseudomonas aeruginosa surface motility and invasion into competing communities enhances interspecies antagonism.
  18. EGFR of platelet regulates macrophage activation and bacterial phagocytosis function.
  19. A Far-Red Fluorescent Probe to Visualize Gram-Positive Bacteria in Patient Samples.
  20. The Tradeoffs Between Persistence and Mutation Rates at Sub-Inhibitory Antibiotic Concentrations in Staphylococcus aureus.
  21. Aged nasal epithelium is more prone to severe COVID-19.
  22. Staphylococcus aureus promotes its intracellular survival by inhibiting Rab11-Rab11FIP4-mediated vesicle trafficking.
  23. Sialic acid-based probiotic intervention in lactating mothers improves the neonatal gut microbiota and immune responses by regulating sialylated milk oligosaccharide synthesis via the gut-breast axis.
  24. Neuronal TLR9 signalling crucial for memory formation.
  25. Identifying ALOX15-initiated lipid peroxidation increases susceptibility to ferroptosis in asthma epithelial cells.
  26. Narrow-spectrum antibiotic exploits metabolic differences to inhibit Pseudomonas aeruginosa.
  27. Mapping the landscape of host-microbiome interactions.
  28. Macrophages need to release the proximal brake to degrade cellular corpses.
  29. Studying Monocyte-Myofibroblast Immunomodulation in a 3D Co-culture System.
  30. Bacterial serotonin induces Treg cells in neonates.
  31. scMoresDB: A comprehensive database of single-cell multi-omics data for human respiratory system.
  32. Revisiting airway epithelial dysfunction and mechanisms in chronic obstructive pulmonary disease: Role of mitochondrial damage.
  33. Bridging systems biology and tissue engineering: Unleashing the full potential of complex 3D in vitro tissue models of disease.
  34. Lactobacilli and Klebsiella: Two Opposites in the Fight for Human Health.
  35. Lactobacillus rhamnosus GG stimulates dietary tryptophan-dependent production of barrier-protecting methylnicotinamide.
  36. Immune Homeostasis: A Novel Example of Teamwork.
  1. Immunol Rev. 2024 Apr 17.
    The potency of hematopoietic stem cell reprogramming for changing immune tone.
    Andrew W Daman, Jin Gyu Cheong, Laura Berneking, Steven Z Josefowicz.
      Innate immune memory endows innate immune cells with antigen independent heightened responsiveness to subsequent challenges. The durability of this response can be mediated by inflammation induced epigenetic and metabolic reprogramming in hematopoietic stem and progenitor cells (HSPCs) that are maintained through differentiation to mature immune progeny. Understanding the mechanisms and extent of trained immunity induction by pathogens and vaccines, such as BCG, in HSPC remains a critical area of exploration with important implications for health and disease. Here we review these concepts and present new analysis to highlight how inflammatory reprogramming of HSPC can potently alter immune tone, including to enhance specific anti-tumor responses. New findings in the field pave the way for novel HSPC targeting therapeutic strategies in cancer and other contexts of immune modulation. Future studies are expected to unravel diverse and extensive effects of infections, vaccines, microbiota, and sterile inflammation on hematopoietic progenitor cells and begin to illuminate the broad spectrum of immunologic tuning that can be established through altering HSPC phenotypes. The purpose of this review is to draw attention to emerging and speculative topics in this field where we posit that focused study of HSPC in the framework of trained immunity holds significant promise.
    Keywords:  PIE‐seq; epigenetics; hematopoietic stem and progenitor cells; inflammatory hematopoiesis; innate immune memory; myelopoiesis; snRNA/ATAC‐seq; trained immunity
    DOI:  https://doi.org/10.1111/imr.13335
  2. Annu Rev Biochem. 2024 Apr 19.
    Soluble Human Lectins at the Host-Microbe Interface.
    Amanda L Peiffer, A E Dugan, L L Kiessling.
      Human lectins are integral to maintaining microbial homeostasis on the skin, in the blood, and at mucosal barriers. These proteins can recognize microbial glycans and inform the host about its microbial status. In accordance with their roles, their production can vary with tissue type. They also can have unique structural and biochemical properties, and they can influence microbial colonization at sites proximal and distal to their tissue of origin. In line with their classification as innate immune proteins, soluble lectins have long been studied in the context of acute infectious disease, but only recently have we begun to appreciate their roles in maintaining commensal microbial communities (i.e., the human microbiota). This review provides an overview of soluble lectins that operate at host-microbe interfaces, their glycan recognition properties, and their roles in physiological and pathological mechanisms.
    DOI:  https://doi.org/10.1146/annurev-biochem-062917-012322
  3. Immunol Rev. 2024 Apr 17.
    Innate immunity-With an adaptive twist.
    Steven Z Josefowicz, Joseph C Sun.
      
    Keywords:  cell lineages and subsets; innate immune memory; innate immunity; innate lymphoid cells; memory; monocytes/macrophages; natural killer cells; trained immunity
    DOI:  https://doi.org/10.1111/imr.13334
  4. Elife. 2024 Apr 19. pii: e89157. [Epub ahead of print]13
    A modified BCG with depletion of enzymes associated with peptidoglycan amidation induces enhanced protection against tuberculosis in mice.
    Moagi Tube Shaku, Peter K Um, Karl L Ocius, Alexis J Apostolos, Marcos M Pires, William R Bishai, Bavesh D Kana.
      Mechanisms by which Mycobacterium tuberculosis (Mtb) evades pathogen recognition receptor activation during infection may offer insights for the development of improved tuberculosis (TB) vaccines. Whilst Mtb elicits NOD-2 activation through host recognition of its peptidoglycan-derived muramyl dipeptide (MDP), it masks the endogenous NOD-1 ligand through amidation of glutamate at the second position in peptidoglycan side-chains. As the current BCG vaccine is derived from pathogenic mycobacteria, a similar situation prevails. To alleviate this masking ability and to potentially improve efficacy of the BCG vaccine, we used CRISPRi to inhibit expression of the essential enzyme pair, MurT-GatD, implicated in amidation of peptidoglycan side-chains. We demonstrate that depletion of these enzymes results in reduced growth, cell wall defects, increased susceptibility to antibiotics, altered spatial localization of new peptidoglycan and increased NOD-1 expression in macrophages. In cell culture experiments, training of a human monocyte cell line with this recombinant BCG yielded improved control of Mtb growth. In the murine model of TB infection, we demonstrate that depletion of MurT-GatD in BCG, which is expected to unmask the D-glutamate diaminopimelate (iE-DAP) NOD-1 ligand, yields superior prevention of TB disease compared to the standard BCG vaccine. In vitro and in vivo experiments in this study demonstrate the feasibility of gene regulation platforms such as CRISPRi to alter antigen presentation in BCG in a bespoke manner that tunes immunity towards more effective protection against TB disease.
    Keywords:  infectious disease; microbiology; mouse
    DOI:  https://doi.org/10.7554/eLife.89157
  5. Nature. 2024 Apr 17.
    Exploring the lung microbiome's role in disease.
    Anthony King.
      
    Keywords:  Microbiology; Microbiome
    DOI:  https://doi.org/10.1038/d41586-024-01123-3
  6. Methods Mol Biol. 2024 ;2782 81-88
    A Robust In Vitro Culture Model and Generation of Memory Monocytes.
    Jing Wang, Shuo Geng, Yajun Wu, Liwu Li.
      Innate monocytes can be trained or reprogrammed to adopt distinct memory states, such as low-grade inflammation and immune exhaustion, bearing fundamental relevance to the pathogenesis of both acute diseases such as sepsis as well as chronic diseases such as atherosclerosis. Therefore, it is critically important to develop a regimen for generating memory monocytes in vitro in order to better define key monocyte memory states with diverse potentials for proliferation, differentiation, and activation, as well as underlying mechanisms. Here, we describe an efficient in vitro system to propagate a large number of highly purified murine memory monocytes through sustaining bone marrow-derived monocytes with macrophage colony-stimulating factor (M-CSF, 10 ng/mL)-containing medium, together with other polarization agents such as lipopolysaccharide (LPS) for a 5-day period. This method can yield high-purity monocytes, capable of exhibiting dynamic memory behaviors upon training with various polarizing agents.
    Keywords:  Bone marrow culture; Exhaustion; Immune memory generation; Model system; Priming
    DOI:  https://doi.org/10.1007/978-1-0716-3754-8_5
  7. J Microbiol. 2024 Apr 18.
    Application of Microbiome-Based Therapies in Chronic Respiratory Diseases.
    Se Hee Lee, Jang Ho Lee, Sei Won Lee.
      The application of microbiome-based therapies in various areas of human disease has recently increased. In chronic respiratory disease, microbiome-based clinical applications are considered compelling options due to the limitations of current treatments. The lung microbiome is ecologically dynamic and affected by various conditions, and dysbiosis is associated with disease severity, exacerbation, and phenotype as well as with chronic respiratory disease endotype. However, it is not easy to directly modulate the lung microbiome. Additionally, studies have shown that chronic respiratory diseases can be improved by modulating gut microbiome and administrating metabolites. Although the composition, diversity, and abundance of the microbiome between the gut and lung are considerably different, modulation of the gut microbiome could improve lung dysbiosis. The gut microbiome influences that of the lung via bacterial-derived components and metabolic degradation products, including short-chain fatty acids. This phenomenon might be associated with the cross-talk between the gut microbiome and lung, called gut-lung axis. There are multiple alternatives to modulate the gut microbiome, such as prebiotics, probiotics, and postbiotics ingestion and fecal material transplantation. Several studies have shown that high-fiber diets, for example, present beneficial effects through the production of short-chain fatty acids. Additionally, genetically modified probiotics to secrete some beneficial molecules might also be utilized to treat chronic respiratory diseases. Further studies on microbial modulation to regulate immunity and potentiate conventional pharmacotherapy will improve microbiome modulation techniques, which will develop as a new therapeutic area in chronic respiratory diseases.
    Keywords:  Asthma; Chronic obstructive pulmonary disease; Gut-lung axis; Idiopathic pulmonary fibrosis; Microbiome
    DOI:  https://doi.org/10.1007/s12275-024-00124-1
  8. bioRxiv. 2024 Apr 03. pii: 2024.04.02.587596. [Epub ahead of print]
    Airway injury induces alveolar epithelial and mesenchymal responses mediated by macrophages.
    Irene G Wong, Jillian Stark, VanNashlee Ya, Aaron L Moye, Alan Baez Vazquez, Susanna M Dang, Andrea Shehaj, Maral J Rouhani, Roderick Bronson, Sam M Janes, Samuel P Rowbotham, Margherita Paschini, Ruth A Franklin, Carla F Kim.
      Acute injury in the airways or the lung activates local progenitors and stimulates changes in cell-cell interactions to restore homeostasis, but it is not appreciated how more distant niches are impacted. We utilized mouse models of airway-specific epithelial injury to examine secondary tissue-wide alveolar, immune, and mesenchymal responses. Single-cell transcriptomics and in vivo validation revealed transient, tissue-wide proliferation of alveolar type 2 (AT2) progenitor cells after club cell-specific ablation. The AT2 cell proliferative response was reliant on alveolar macrophages (AMs) via upregulation of Spp1 which encodes the secreted factor Osteopontin. A previously uncharacterized mesenchymal population we termed Mesenchymal Airway/Adventitial Niche Cell 2 (MANC2) also exhibited dynamic changes in abundance and a pro-fibrotic transcriptional signature after club cell ablation in an AM-dependent manner. Overall, these results demonstrate that acute airway damage can trigger distal lung responses including altered cell-cell interactions that may contribute to potential vulnerabilities for further dysregulation and disease.Highlights: - Airway epithelial cell injury causes proliferation of AT2 cells, the alveolar epithelial progenitor cells - Alveolar macrophages promote AT2 cell proliferation after airway injury via upregulation of Spp1 - Alveolar macrophages have a pro-fibrotic effect on lung mesenchyme after airway injury- Damage to one epithelial compartment can elicit altered epithelial-immune-mesenchymal cell crosstalk in another compartment of the same tissue.
    DOI:  https://doi.org/10.1101/2024.04.02.587596
  9. Infect Immun. 2024 Apr 17. e0044723
    Bacterial surface lipoproteins mediate epithelial microinvasion by Streptococcus pneumoniae.
    Jia Mun Chan, Elisa Ramos-Sevillano, Modupeh Betts, Holly U Wilson, Caroline M Weight, Ambrine Houhou-Ousalah, Gabriele Pollara, Jeremy S Brown, Robert S Heyderman.
      Streptococcus pneumoniae, a common colonizer of the upper respiratory tract, invades nasopharyngeal epithelial cells without causing disease in healthy participants of controlled human infection studies. We hypothesized that surface expression of pneumococcal lipoproteins, recognized by the innate immune receptor TLR2, mediates epithelial microinvasion. Mutation of lgt in serotype 4 (TIGR4) and serotype 6B (BHN418) pneumococcal strains abolishes the ability of the mutants to activate TLR2 signaling. Loss of lgt also led to the concomitant decrease in interferon signaling triggered by the bacterium. However, only BHN418 lgt::cm but not TIGR4 lgt::cm was significantly attenuated in epithelial adherence and microinvasion compared to their respective wild-type strains. To test the hypothesis that differential lipoprotein repertoires in TIGR4 and BHN418 lead to the intraspecies variation in epithelial microinvasion, we employed a motif-based genome analysis and identified an additional 525 a.a. lipoprotein (pneumococcal accessory lipoprotein A; palA) encoded by BHN418 that is absent in TIGR4. The gene encoding palA sits within a putative genetic island present in ~10% of global pneumococcal isolates. While palA was enriched in the carriage and otitis media pneumococcal strains, neither mutation nor overexpression of the gene encoding this lipoprotein significantly changed microinvasion patterns. In conclusion, mutation of lgt attenuates epithelial inflammatory responses during pneumococcal-epithelial interactions, with intraspecies variation in the effect on microinvasion. Differential lipoprotein repertoires encoded by the different strains do not explain these differences in microinvasion. Rather, we postulate that post-translational modifications of lipoproteins may account for the differences in microinvasion.IMPORTANCEStreptococcus pneumoniae (pneumococcus) is an important mucosal pathogen, estimated to cause over 500,000 deaths annually. Nasopharyngeal colonization is considered a necessary prerequisite for disease, yet many people are transiently and asymptomatically colonized by pneumococci without becoming unwell. It is therefore important to better understand how the colonization process is controlled at the epithelial surface. Controlled human infection studies revealed the presence of pneumococci within the epithelium of healthy volunteers (microinvasion). In this study, we focused on the regulation of epithelial microinvasion by pneumococcal lipoproteins. We found that pneumococcal lipoproteins induce epithelial inflammation but that differing lipoprotein repertoires do not significantly impact the magnitude of microinvasion. Targeting mucosal innate immunity and epithelial microinvasion alongside the induction of an adaptive immune response may be effective in preventing pneumococcal colonization and disease.
    Keywords:  Streptococcus pneumoniae; bacterial lipoproteins; epithelium; host-microbe interactions; microinvasion
    DOI:  https://doi.org/10.1128/iai.00447-23
  10. Cell Chem Biol. 2024 Apr 15. pii: S2451-9456(24)00125-9. [Epub ahead of print]
    Strategies of bacterial detection by inflammasomes.
    Jordan B Jastrab, Jonathan C Kagan.
      Mammalian innate immunity is regulated by pattern-recognition receptors (PRRs) and guard proteins, which use distinct strategies to detect infections. PRRs detect bacterial molecules directly, whereas guards detect host cell manipulations by microbial virulence factors. Despite sensing infection through different mechanisms, both classes of innate immune sensors can activate the inflammasome, an immune complex that can mediate cell death and inflammation. Inflammasome-mediated immune responses are crucial for host defense against many bacterial pathogens and prevent invasion by non-pathogenic organisms. In this review, we discuss the mechanisms by which inflammasomes are stimulated by PRRs and guards during bacterial infection, and the strategies used by virulent bacteria to evade inflammasome-mediated immunity.
    DOI:  https://doi.org/10.1016/j.chembiol.2024.03.009
  11. Exp Cell Res. 2024 Apr 16. pii: S0014-4827(24)00143-5. [Epub ahead of print] 114052
    Dihydroartemisinin is an inhibitor of trained immunity through Akt/mTOR/HIF1α signaling pathway.
    Yu Gao, Zhen-Zhen Liu, Jia-Bao Zhang, Cheng-Kai Zhou, Jian-Gang Zhang, Xiao-Qi Lin, Qi Yin, Wei Chen, Yong-Jun Yang.
      Trained immunity is mechanistically defined as the metabolically and epigenetically mediated long-term functional adaptation of the innate immune system, characterized by a heightened response to a secondary stimulation. Given appropriate activation, trained immunity represents an attractive anti-infective therapeutic target. Nevertheless, excessive immune response and subsequent inflammatory cascades may contribute to pathological tissue damage, indicating that the negative impacts of trained immunity appear to be significant. In this study, we show that innate immune responses such as the production of extracellular traps, pro-inflammatory cytokines, and autophagy-related proteins were markedly augmented in trained BMDMs. Furthermore, heat-killed C. albicans priming promotes the activation of the AIM2 inflammasome, and AIM2-/- mice exhibit impaired memory response induced by heat-killed C. albicans. Therefore, we establish that the AIM2 inflammasome is involved in trained immunity and emerges as a promising therapeutic target for potentially deleterious effects. Dihydroartemisinin can inhibit the memory response induced by heat-killed C. albicans through modulation of mTOR signaling and the AIM2 inflammasome. The findings suggest that dihydroartemisinin can reduce the induction of trained immunity by heat-killed C. albicans in C57BL/6 mice. Dihydroartemisinin is one such therapeutic intervention that has the potential to treat of diseases characterized by excessive trained immunity.
    Keywords:  AIM2 inflammasome; C. perfringens; autophagy; dihydroartemisinin; inhibitor; trained immunity
    DOI:  https://doi.org/10.1016/j.yexcr.2024.114052
  12. Respir Res. 2024 Apr 16. 25(1): 165
    Human genetic associations of the airway microbiome in chronic obstructive pulmonary disease.
    Jingyuan Gao, Yuqiong Yang, Xiaopeng Xiang, Huimin Zheng, Xinzhu Yi, Fengyan Wang, Zhenyu Liang, Dandan Chen, Weijuan Shi, Lingwei Wang, Di Wu, Shengchuan Feng, Qiaoyun Huang, Xueping Li, Wensheng Shu, Rongchang Chen, Nanshan Zhong, Zhang Wang.
      Little is known about the relationships between human genetics and the airway microbiome. Deeply sequenced airway metagenomics, by simultaneously characterizing the microbiome and host genetics, provide a unique opportunity to assess the microbiome-host genetic associations. Here we performed a co-profiling of microbiome and host genetics with the identification of over 5 million single nucleotide polymorphisms (SNPs) through deep metagenomic sequencing in sputum of 99 chronic obstructive pulmonary disease (COPD) and 36 healthy individuals. Host genetic variation was the most significant factor associated with the microbiome except for geography and disease status, with its top 5 principal components accounting for 12.11% of the microbiome variability. Within COPD individuals, 113 SNPs mapped to candidate genes reported as genetically associated with COPD exhibited associations with 29 microbial species and 48 functional modules (P < 1 × 10-5), where Streptococcus salivarius exhibits the strongest association to SNP rs6917641 in TBC1D32 (P = 9.54 × 10-8). Integration of concurrent host transcriptomic data identified correlations between the expression of host genes and their genetically-linked microbiome features, including NUDT1, MAD1L1 and Veillonella parvula, TTLL9 and Stenotrophomonas maltophilia, and LTA4H and Haemophilus influenzae. Mendelian randomization analyses revealed a potential causal link between PARK7 expression and microbial type III secretion system, and a genetically-mediated association between COPD and increased relative abundance of airway Streptococcus intermedius. These results suggest a previously underappreciated role of host genetics in shaping the airway microbiome and provide fresh hypotheses for genetic-based host-microbiome interactions in COPD.
    Keywords:  Airway microbiome; COPD; GWAS; Mendelian randomization; Microbiome-host genetic interaction
    DOI:  https://doi.org/10.1186/s12931-024-02805-2
  13. Nature. 2024 Apr 17.
    Bacteria deploy umbrella toxins against their competitors.
    Sarah J Coulthurst.
      
    Keywords:  Infection; Microbiology
    DOI:  https://doi.org/10.1038/d41586-024-01016-5
  14. bioRxiv. 2024 Apr 02. pii: 2024.04.01.587641. [Epub ahead of print]
    Single-cell transcriptional landscape of temporal neutrophil response to burn wound in larval zebrafish.
    Yiran Hou, Parth Khatri, Julie Rindy, Zachery Schultz, Anqi Gao, Zhili Chen, Angela Lf Gibson, Anna Huttenlocher, Huy Q Dinh.
      Neutrophils accumulate early in tissue injury. However, the cellular and functional heterogeneity of neutrophils during homeostasis and in response to tissue damage remains unclear. Here, we use larval zebrafish to understand neutrophil responses to thermal injury. Single-cell transcriptional mapping of myeloid cells during a 3-day time course in burn and control larvae revealed distinct neutrophil subsets and their cell-cell interactions with macrophages across time and conditions. The trajectory formed by three zebrafish neutrophil subsets resembles human neutrophil maturation, with varying transition patterns between conditions. Through ligand-receptor cell-cell interaction analysis, we found neutrophils communicate more in burns in a pathway and temporal manner. Finally, we identified the correlation between zebrafish myeloid signatures and human burn severity, establishing GPR84+ neutrophils as a potential marker of early innate immune response in burns. This work builds the molecular foundation and a comparative single-cell genomic framework to identify neutrophil markers of tissue damage using model organisms.
    DOI:  https://doi.org/10.1101/2024.04.01.587641
  15. Front Cell Infect Microbiol. 2024 ;14 1377012
    Current progresses and challenges for microbiome research in human health: a perspective.
    Simone Filardo, Marisa Di Pietro, Rosa Sessa.
      It is becoming increasingly clear that the human microbiota, also known as "the hidden organ", possesses a pivotal role in numerous processes involved in maintaining the physiological functions of the host, such as nutrient extraction, biosynthesis of bioactive molecules, interplay with the immune, endocrine, and nervous systems, as well as resistance to the colonization of potential invading pathogens. In the last decade, the development of metagenomic approaches based on the sequencing of the bacterial 16s rRNA gene via Next Generation Sequencing, followed by whole genome sequencing via third generation sequencing technologies, has been one of the great advances in molecular biology, allowing a better profiling of the human microbiota composition and, hence, a deeper understanding of the importance of microbiota in the etiopathogenesis of different pathologies. In this scenario, it is of the utmost importance to comprehensively characterize the human microbiota in relation to disease pathogenesis, in order to develop novel potential treatment or preventive strategies by manipulating the microbiota. Therefore, this perspective will focus on the progress, challenges, and promises of the current and future technological approaches for microbiome profiling and analysis.
    Keywords:  16s metagenomic; human microbiome; metabolomics; multi-omics; proteomics; transcriptomics; whole genome sequencing
    DOI:  https://doi.org/10.3389/fcimb.2024.1377012
  16. Cell Rep. 2024 Apr 11. pii: S2211-1247(24)00422-4. [Epub ahead of print]43(4): 114094
    Squalene-epoxidase-catalyzed 24(S),25-epoxycholesterol synthesis promotes trained-immunity-mediated antitumor activity.
    Yongxiang Liu, Zifeng Wang, Huan Jin, Lei Cui, Bitao Huo, Chunyuan Xie, Jiahui Li, Honglu Ding, Huanling Zhang, Wenjing Xiong, Mengyun Li, Hongxia Zhang, Hui Guo, Chunwei Li, Tiantian Wang, Xiaojuan Wang, Wenzhuo He, Zining Wang, Jin-Xin Bei, Peng Huang, Jinyun Liu, Xiaojun Xia.
      The importance of trained immunity in antitumor immunity has been increasingly recognized, but the underlying metabolic regulation mechanisms remain incompletely understood. In this study, we find that squalene epoxidase (SQLE), a key enzyme in cholesterol synthesis, is required for β-glucan-induced trained immunity in macrophages and ensuing antitumor activity. Unexpectedly, the shunt pathway, but not the classical cholesterol synthesis pathway, catalyzed by SQLE, is required for trained immunity induction. Specifically, 24(S),25-epoxycholesterol (24(S),25-EC), the shunt pathway metabolite, activates liver X receptor and increases chromatin accessibility to evoke innate immune memory. Meanwhile, SQLE-induced reactive oxygen species accumulation stabilizes hypoxia-inducible factor 1α protein for metabolic switching into glycolysis. Hence, our findings identify 24(S),25-EC as a key metabolite for trained immunity and provide important insights into how SQLE regulates trained-immunity-mediated antitumor activity.
    Keywords:  24(S),25-epoxycholesterol; CP: Cancer; CP: Immunology; antitumor immunity; reactive oxygen species; squalene epoxidase; trained immunity
    DOI:  https://doi.org/10.1016/j.celrep.2024.114094
  17. bioRxiv. 2024 Apr 04. pii: 2024.04.03.588010. [Epub ahead of print]
    Pseudomonas aeruginosa surface motility and invasion into competing communities enhances interspecies antagonism.
    Andrea Sánchez-Peña, James B Winans, Carey D Nadell, Dominique H Limoli.
      Chronic polymicrobial infections involving Pseudomonas aeruginosa and Staphylococcus aureus are prevalent, difficult to eradicate, and associated with poor health outcomes. Therefore, understanding interactions between these pathogens is important to inform improved treatment development. We previously demonstrated that P. aeruginosa is attracted to S. aureus using type IV pili-mediated chemotaxis, but the impact of attraction on S. aureus growth and physiology remained unknown. Using live single-cell confocal imaging to visualize microcolony structure, spatial organization, and survival of S. aureus during coculture, we found that interspecies chemotaxis provides P. aeruginosa a competitive advantage by promoting invasion into and disruption of S. aureus microcolonies. This behavior renders S. aureus susceptible to P. aeruginosa antimicrobials. Conversely, in the absence of type IV pilus motility, P. aeruginosa cells exhibit reduced invasion of S. aureus colonies. Instead, P. aeruginosa builds a cellular barrier adjacent to S. aureus and secretes diffusible, bacteriostatic antimicrobials like 2-heptyl-4-hydroxyquinoline- N -oxide (HQNO) into the S. aureus colonies. P. aeruginosa reduced invasion leads to the formation of denser and thicker S. aureus colonies with significantly increased HQNO-mediated lactic acid fermentation, a physiological change that could complicate the effective treatment of infections. Finally, we show that P. aeruginosa motility modifications of spatial structure enhance competition against S. aureus . Overall, these studies build on our understanding of how P. aeruginosa type IV pili-mediated interspecies chemotaxis mediates polymicrobial interactions, highlighting the importance of spatial positioning in mixed-species communities.
    DOI:  https://doi.org/10.1101/2024.04.03.588010
  18. J Inflamm (Lond). 2024 Apr 17. 21(1): 10
    EGFR of platelet regulates macrophage activation and bacterial phagocytosis function.
    Shuhua Luo, Riping Xu, Pengyun Xie, Xiaolei Liu, Chunxiu Ling, Yusha Liu, Xuedi Zhang, Zhengyuan Xia, Zhanghui Chen, Jing Tang.
      BACKGROUND: Beyond their crucial role in hemostasis, platelets possess the ability to regulate inflammation and combat infections through various mechanisms. Stringent control of macrophage activation is essential during innate immune responses in sepsis. Macrophages are considered crucial phagocytic cells that aid in the elimination of pathogens. Platelet interactions with monocytes-macrophages are known to be significant in the response against bacterial infections, but the primary mediator driving these interactions remains unclear. EGFR plays critical role in the regulation of inflammation and infection through various mechanisms.RESULTS: The overexpression of platelets by thrombopoietin (TPO) leads to the sequestration of both pro-inflammatory (IL-6/IL-1) and anti-inflammatory (IL-10) cytokines in the organ tissue of septic mice. Epidermal growth factor receptor (EGFR) is critical for platelet activation in sepsis. EGFR-licensed platelets enhance macrophage immune function, including the production of reactive oxygen species (ROS) and the clearance of bacteria. Platelet EGFR also induces M1 macrophage polarization by increasing the expression of inducible nitric oxide synthase (iNOS) and CD64.
    CONCLUSION: EGFR can activate platelet immune function. Moreover, activated platelets efficiently regulate bacterial phagocytosis and pro-inflammatory function of macrophages through an EGFR-dependent pathway.
    Keywords:  EGFR; Macrophage; Phagocytosis; Platelet; Pyroptosis; Sepsis
    DOI:  https://doi.org/10.1186/s12950-024-00382-1
  19. ACS Infect Dis. 2024 Apr 17.
    A Far-Red Fluorescent Probe to Visualize Gram-Positive Bacteria in Patient Samples.
    Krittapas Jantarug, Vishwachi Tripathi, Benedict Morin, Aya Iizuka, Richard Kuehl, Mario Morgenstern, Martin Clauss, Nina Khanna, Dirk Bumann, Pablo Rivera-Fuentes.
      Gram-positive bacteria, in particular Staphylococcus aureus (S. aureus), are the leading bacterial cause of death in high-income countries and can cause invasive infections at various body sites. These infections are associated with prolonged hospital stays, a large economic burden, considerable treatment failure, and high mortality rates. So far, there is only limited knowledge about the specific locations where S. aureus resides in the human body during various infections. Hence, the visualization of S. aureus holds significant importance in microbiological research. Herein, we report the development and validation of a far-red fluorescent probe to detect Gram-positive bacteria, with a focus on staphylococci, in human biopsies from deep-seated infections. This probe displays strong fluorescence and low background in human tissues, outperforming current tools for S. aureus detection. Several applications are demonstrated, including fixed- and live-cell imaging, flow cytometry, and super-resolution bacterial imaging.
    Keywords:  Gram-positive; S. aureus; fluorescent probe; imaging; super-resolution microscopy; vancomycin
    DOI:  https://doi.org/10.1021/acsinfecdis.4c00060
  20. bioRxiv. 2024 Apr 01. pii: 2024.04.01.587561. [Epub ahead of print]
    The Tradeoffs Between Persistence and Mutation Rates at Sub-Inhibitory Antibiotic Concentrations in Staphylococcus aureus.
    Alysha S Ismail, Brandon A Berryhill, Teresa Gil-Gil, Joshua A Manuel, Andrew P Smith, Fernando Baquero, Bruce R Levin.
      The rational design of the antibiotic treatment of bacterial infections employs these drugs to reach concentrations that exceed the minimum needed to prevent the replication of the target bacteria. However, within a treated patient, spatial and physiological heterogeneity promotes antibiotic gradients such that the concentration of antibiotics at specific sites is below the minimum needed to inhibit bacterial growth. Here, we investigate the effects of sub-inhibitory antibiotic concentrations on three parameters central to bacterial infection and the success of antibiotic treatment, using in vitro experiments with Staphylococcus aureus and mathematical-computer simulation models. Our results, using drugs of six different classes, demonstrate that exposure to sub-inhibitory antibiotic concentrations not only alters the dynamics of bacterial growth but also increases the mutation rate to antibiotic resistance and decreases the rate of production of persister cells thereby reducing the persistence level. Understanding this trade-off between mutation rates and persistence levels resulting from sub-inhibitory antibiotic exposure is crucial for optimizing, and mitigating the failure of, antibiotic therapy.
    Keywords:  Antibiotics; antibiotic resistance mutation rate; bacterial persistence; minimum inhibitory concentration; pharmacodynamics; population biology
    DOI:  https://doi.org/10.1101/2024.04.01.587561
  21. Nat Immunol. 2024 Apr 19.
    Aged nasal epithelium is more prone to severe COVID-19.
    Ivan Zanoni.
      
    DOI:  https://doi.org/10.1038/s41590-024-01824-x
  22. Vet Microbiol. 2024 Apr 12. pii: S0378-1135(24)00113-5. [Epub ahead of print]293 110091
    Staphylococcus aureus promotes its intracellular survival by inhibiting Rab11-Rab11FIP4-mediated vesicle trafficking.
    Huiling Xu, Xiaozhou Wang, Zhizhong Zhang, Jiaqing Hu, Yongtao Yu, Jiandong Wang, Yongxia Liu, Jianzhu Liu.
      Mastitis in dairy cows is mainly caused by bacteria, in which Staphylococcus aureus appears frequently. Epithelial cells, as a major physical barrier of mammary gland, play an important role in preventing mastitis in dairy cows. Our previous study reported that Rab11fip4 (an effector of Rab11) was significantly changed in response to stimulation by S. aureus. So, in this study, the role of Rab11A in phagocytosis of bovine mammary epithelial cells (MAC-T) against S. aureus was evaluated. First, changes of Rab11A and Rab11fip4 were analyzed in response to S. aureus by immunofluorescence and western blotting. Subsequently, the effects of Rab11A and Rab11fip4 on proliferation of S. aureus, as well as formation and function of late endosomes (LEs) and lysosomes (LYSs) were investigated. The results showed that, after infection, Rab11A and Rab11fip4 were recruited to phagosomes containing S. aureus. Rab11A promoted bacterial clearance and rescues the destruction of LEs and LYSs by S. aureus, whereas Rab11fip4 did the opposite. These findings provide new insights into phagocytosis and control of S. aureus in host cells, thus lay the foundation to elucidate the pathogenesis of S. aureus in bovine mastitis.
    Keywords:  Bovine mammary epithelial cells; Bovine mastitis; Phagosome; Rab11A; Staphylococcus aureus
    DOI:  https://doi.org/10.1016/j.vetmic.2024.110091
  23. Gut Microbes. 2024 Jan-Dec;16(1):16(1): 2334967
    Sialic acid-based probiotic intervention in lactating mothers improves the neonatal gut microbiota and immune responses by regulating sialylated milk oligosaccharide synthesis via the gut-breast axis.
    Yushuang Wang, Binqi Rui, Xiaolei Ze, Yujia Liu, Da Yu, Yinhui Liu, Zhi Li, Yu Xi, Xixi Ning, Zengjie Lei, Jieli Yuan, Liang Li, Xuguang Zhang, Wenzhe Li, Yanjie Deng, Jingyu Yan, Ming Li.
      Human milk oligosaccharides (HMOs) are vital milk carbohydrates that help promote the microbiota-dependent growth and immunity of infants. Sialic acid (SA) is a crucial component of sialylated milk oligosaccharides (S-MOs); however, the effects of SA supplementation in lactating mothers on S-MO biosynthesis and their breastfed infants are unknown. Probiotic intervention during pregnancy or lactation demonstrates promise for modulating the milk glycobiome. Here, we evaluated whether SA and a probiotic (Pro) mixture could increase S-MO synthesis in lactating mothers and promote the microbiota development of their breastfed neonates. The results showed that SA+Pro intervention modulated the gut microbiota and 6'-SL contents in milk of maternal rats more than the SA intervention, which promoted Lactobacillus reuteri colonization in neonates and immune development. Deficient 6'-SL in the maternal rat milk of St6gal1 knockouts (St6gal1-/-) disturbed intestinal microbial structures in their offspring, thereby impeding immune tolerance development. SA+Pro intervention in lactating St6gal1± rats compromised the allergic responses of neonates by promoting 6'-SL synthesis and the neonatal gut microbiota. Our findings from human mammary epithelial cells (MCF-10A) indicated that the GPR41-PI3K-Akt-PPAR pathway helped regulate 6'-SL synthesis in mammary glands after SA+Pro intervention through the gut - breast axis. We further validated our findings using a human-cohort study, confirming that providing SA+Pro to lactating Chinese mothers increased S-MO contents in their breast milk and promoted gut Bifidobacterium spp. and Lactobacillus spp. colonization in infants, which may help enhance immune responses. Collectively, our findings may help alter the routine supplementation practices of lactating mothers to modulate milk HMOs and promote the development of early-life gut microbiota and immunity.
    Keywords:  Sialic acid; gut microbiota; gut–breast axis; immune response; infant; milk oligosaccharide; probiotic
    DOI:  https://doi.org/10.1080/19490976.2024.2334967
  24. Nat Rev Immunol. 2024 Apr 17.
    Neuronal TLR9 signalling crucial for memory formation.
    Alexandra Flemming.
      
    DOI:  https://doi.org/10.1038/s41577-024-01034-4
  25. Biochim Biophys Acta Mol Basis Dis. 2024 Apr 17. pii: S0925-4439(24)00165-0. [Epub ahead of print] 167176
    Identifying ALOX15-initiated lipid peroxidation increases susceptibility to ferroptosis in asthma epithelial cells.
    Weizhen Zhang, Fangfang Huang, Xuexuan Ding, Jingtong Qin, Wenjian Wang, Lianxiang Luo.
      Ferroptosis is a programmed form of cell death regulated by iron and has been linked to the development of asthma. However, the precise mechanisms driving ferroptosis in asthma remain elusive. To gain deeper insights, we conducted an analysis of nasal epithelial and sputum samples from the GEO database using three machine learning methods. Our investigation identified a pivotal gene, Arachidonate 15-lipoxygenase (ALOX15), associated with ferroptosis in asthma. Through both in vitro and in vivo experiments, we further confirmed the significant role of ALOX15 in ferroptosis in asthma. Our results demonstrate that ferroptosis manifests in an HDM/LPS-induced allergic airway inflammation (AAI) mouse model, mimicking human asthma, and in HDM/LPS-stimulated 16HBE cells. Moreover, we observed an up-regulation of ALOX15 expression in HDM/LPS-induced mice and cells. Notably, silencing ALOX15 markedly decreased HDM/LPS-induced ferroptosis in 16HBE cells. These findings indicate that ferroptosis may be implicated in the onset and progression of asthma, with ALOX15-induced lipid peroxidation raising the susceptibility to ferroptosis in asthmatic epithelial cells.
    Keywords:  ALOX15; Asthma; Ferroptosis; Lipid peroxidation; PEBP1
    DOI:  https://doi.org/10.1016/j.bbadis.2024.167176
  26. Nat Microbiol. 2024 Apr 19.
    Narrow-spectrum antibiotic exploits metabolic differences to inhibit Pseudomonas aeruginosa.
      
    DOI:  https://doi.org/10.1038/s41564-024-01673-2
  27. Nat Biotechnol. 2024 Apr;42(4): 571
    Mapping the landscape of host-microbiome interactions.
    Iris Marchal.
      
    DOI:  https://doi.org/10.1038/s41587-024-02219-x
  28. Nat Struct Mol Biol. 2024 Apr;31(4): 586
    Macrophages need to release the proximal brake to degrade cellular corpses.
    Dimitris Typas.
      
    DOI:  https://doi.org/10.1038/s41594-024-01305-7
  29. Methods Mol Biol. 2024 ;2782 97-112
    Studying Monocyte-Myofibroblast Immunomodulation in a 3D Co-culture System.
    Avi Petroff.
      Simple and reproducible 3D cell culture systems that mimic biological interactions within physiological tissues (biomimetics) can provide unique insight for scientific inquiries compared to 2D cell cultures. Fibroblast-populated collagen lattices (FPCLs) are commonly used for mimicking physiological collagen matrices, potentiating biomechanical stresses on embedded fibroblasts. Here, we describe a novel 3D co-culture model that incorporates human Tenon's capsule fibroblasts embedded in FPCLs co-cultured with THP-1 monocytes suspended in culture media. This method can be used for the assessment of cell-cell interactions in various stages of the wound healing process and can facilitate various types of immune cells in co-culture. This system can also be used to study pharmacological agents that may eventually improve clinical outcomes in patients affected by inflammatory disorders.
    Keywords:  3D Model; Co-culture; Fibrosis; Glaucoma; Inflammation; Monocytes; Myofibroblasts
    DOI:  https://doi.org/10.1007/978-1-0716-3754-8_7
  30. Nat Rev Immunol. 2024 Apr 17.
    Bacterial serotonin induces Treg cells in neonates.
    Alexandra Flemming.
      
    DOI:  https://doi.org/10.1038/s41577-024-01033-5
  31. iScience. 2024 Apr 19. 27(4): 109567
    scMoresDB: A comprehensive database of single-cell multi-omics data for human respiratory system.
    Kang Chen, Yutong Han, Yanni Wang, Dingli Zhou, Fanjie Wu, Wenhao Cai, Shikang Zheng, Qinyuan Xiao, Haiyue Zhang, Weizhong Li.
      The human respiratory system is a complex and important system that can suffer a variety of diseases. Single-cell sequencing technologies, applied in many respiratory disease studies, have enhanced our ability in characterizing molecular and phenotypic features at a single-cell resolution. The exponentially increasing data from these studies have consequently led to difficulties in data sharing and analysis. Here, we present scMoresDB, a single-cell multi-omics database platform with extensive omics types tailored for human respiratory diseases. scMoresDB re-analyzes single-cell multi-omics datasets, providing a user-friendly interface with cross-omics search capabilities, interactive visualizations, and analytical tools for comprehensive data sharing and integrative analysis. Our example applications highlight the potential significance of BSG receptor in SARS-CoV-2 infection as well as the involvement of HHIP and TGFB2 in the development and progression of chronic obstructive pulmonary disease. scMoresDB significantly increases accessibility and utility of single-cell data relevant to human respiratory system and associated diseases.
    Keywords:  Biological database; Body system; Data processing in systems biology; Human; Transcriptomics
    DOI:  https://doi.org/10.1016/j.isci.2024.109567
  32. Am J Physiol Lung Cell Mol Physiol. 2024 Apr 16.
    Revisiting airway epithelial dysfunction and mechanisms in chronic obstructive pulmonary disease: Role of mitochondrial damage.
    Qinglan He, Peijun Li, Lihua Han, Chen Yang, Meiling Jiang, Yingqi Wang, Xiaoyu Han, Yuanyuan Cao, Xiaodan Liu, Weibing Wu.
      Chronic exposure to environmental hazards causes airway epithelial dysfunction, primarily impaired physical barriers, immune dysfunction, and repair or regeneration. Impairment of airway epithelial function subsequently leads to exaggerated airway inflammation and remodeling, the main features of chronic obstructive pulmonary disease (COPD). Mitochondrial damage has been identified as one of the mechanisms of airway abnormalities in COPD, which is closely related to airway inflammation and airflow limitation. In this review, we evaluate updated evidence for airway epithelial mitochondrial damage in COPD and focus on the role of mitochondrial damage in airway epithelial dysfunction. In addition, the possible mechanism of airway epithelial dysfunction mediated by mitochondrial damage is discussed in detail, and recent strategies related to airway epithelial-targeted mitochondrial therapy are summarized. Results have shown that dysregulation of mitochondrial quality and oxidative stress may lead to airway epithelial dysfunction in COPD. This may result from mitochondrial damage as a central organelle mediating abnormalities in cellular metabolism. Mitochondrial damage mediates pro-cellular senescence effects due to mitochondrial reactive oxygen species, which effectively exacerbate different types of programmed cell death, participate in lipid metabolism abnormalities, and ultimately promote airway epithelial dysfunction and trigger COPD airway abnormalities. These can be prevented by targeting mitochondrial damage factors and mitochondrial transfer. Thus, because mitochondrial damage is involved in COPD progression as a central factor of homeostatic imbalance in airway epithelial cells, it may be a novel target for therapeutic intervention to restore airway epithelial integrity and function in COPD.
    Keywords:  airway epithelial dysfunction; chronic obstructive pulmonary disease; mechanisms; mitochondrial
    DOI:  https://doi.org/10.1152/ajplung.00362.2023
  33. Biophys Rev (Melville). 2024 Jun;5(2): 021301
    Bridging systems biology and tissue engineering: Unleashing the full potential of complex 3D in vitro tissue models of disease.
    Jose L Cadavid, Nancy T Li, Alison P McGuigan.
      Rapid advances in tissue engineering have resulted in more complex and physiologically relevant 3D in vitro tissue models with applications in fundamental biology and therapeutic development. However, the complexity provided by these models is often not leveraged fully due to the reductionist methods used to analyze them. Computational and mathematical models developed in the field of systems biology can address this issue. Yet, traditional systems biology has been mostly applied to simpler in vitro models with little physiological relevance and limited cellular complexity. Therefore, integrating these two inherently interdisciplinary fields can result in new insights and move both disciplines forward. In this review, we provide a systematic overview of how systems biology has been integrated with 3D in vitro tissue models and discuss key application areas where the synergies between both fields have led to important advances with potential translational impact. We then outline key directions for future research and discuss a framework for further integration between fields.
    DOI:  https://doi.org/10.1063/5.0179125
  34. Biochemistry (Mosc). 2024 Jan;89(Suppl 1): S71-S89
    Lactobacilli and Klebsiella: Two Opposites in the Fight for Human Health.
    Leonid A Shaposhnikov, Vladimir I Tishkov, Anastasia A Pometun.
      The problem of antibiotic resistance is currently very acute. Numerous research and development of new antibacterial drugs are being carried out that could help cope with various infectious agents. One of the promising directions for the search for new antibacterial drugs is the search among the probiotic strains present in the human gastrointestinal tract. This review is devoted to characteristics of one of these probiotic strains that have been studied to date: Limosilactobacillus reuteri. The review discusses its properties, synthesis of various compounds, as well as role of this strain in modulating various systems of the human body. The review also examines key characteristics of one of the most harmful among the currently known pathogenic organisms, Klebsiella, which is significantly resistant to antibiotics existing in medical practice, and also poses a great threat of nosocomial infections. Discussion of characteristics of the two strains, which have opposite effects on human health, may help in creation of new effective antibacterial drugs without significant side effects.
    Keywords:  Klebsiella; Limosilactobacillus reuteri; antibiotic resistance; lactobacilli
    DOI:  https://doi.org/10.1134/S0006297924140050
  35. Cell Mol Gastroenterol Hepatol. 2024 Apr 17. pii: S2352-345X(24)00094-8. [Epub ahead of print]
    Lactobacillus rhamnosus GG stimulates dietary tryptophan-dependent production of barrier-protecting methylnicotinamide.
    Panan Suntornsaratoon, Jayson M Antonio, Juan Flores, Ravij Upadhyay, John Veltri, Sheila Bandyopadhyay, Rhema Dadala, Michael Kim, Yue Liu, Iyshwarya Balasubramanian, Jerrold R Turner, Xiaoyang Su, Wei Vivian Li, Nan Gao, Ronaldo P Ferraris.
      BACKGROUND & AIMS: Lacticaseibacillus rhamnosus GG (LGG) is the world's most consumed probiotic but its mechanism of action on intestinal permeability and differentiation along with its interactions with an essential source of signaling metabolites, dietary tryptophan, are unclear.METHODS: Untargeted metabolomic and transcriptomic analyses were performed in LGG mono-colonized germ-free (GF) mice fed tryptophan (trp)-free or -sufficient diets. LGG-derived metabolites were profiled in vitro under anaerobic and aerobic conditions. Multiomic correlations using a newly developed algorithm discovered novel metabolites tightly linked to tight junction (TJ) and cell differentiation genes whose abundances were regulated by LGG and dietary trp. Barrier-modulation by these metabolites were functionally tested in Caco2 cells, mouse enteroids, and dextran sulfate sodium (DSS) experimental colitis. The contribution of these metabolites to barrier protection is delineated at specific TJ proteins and enterocyte-promoting factors with gain and loss of function approaches.
    RESULTS: LGG, strictly with dietary trp, promotes the enterocyte program and expression of TJ genes, particularly Ocln. Functional evaluations of fecal and serum metabolites synergistically stimulated by LGG and trp revealed a novel Vitamin B3 metabolism pathway, with methylnicotinamide (MNA) unexpectedly being the most robust barrier-protective metabolite in vitro and in vivo. Reduced serum MNA is significantly associated with increased disease activity in IBD patients. Exogenous MNA enhances gut barrier in homeostasis and robustly promotes colonic healing in DSS colitis. MNA is sufficient to promote intestinal epithelial Ocln and RNF43, a master inhibitor of Wnt. Blocking trp or Vitamin B3 absorption abolishes barrier recovery in vivo.
    CONCLUSIONS: Our study uncovers a novel LGG-regulated dietary trp-dependent production of MNA that protects the gut barrier against colitis.
    Keywords:  (not in title): metabolome; probiotic; tight junction; transcriptome
    DOI:  https://doi.org/10.1016/j.jcmgh.2024.04.003
  36. Methods Mol Biol. 2024 ;2782 1-24
    Immune Homeostasis: A Novel Example of Teamwork.
    Vijay Kumar, John H Stewart.
      All living organisms must maintain homeostasis to survive, reproduce, and pass their traits on to the next generation. If homeostasis is not maintained, it can result in various diseases and ultimately lead to death. Physiologists have coined the term "homeostasis" to describe this process. With the emergence of immunology as a separate branch of medicine, the concept of immune homeostasis has been introduced. Maintaining immune homeostasis is crucial to support overall homeostasis through different immunological and non-immunological routes. Any changes in the immune system can lead to chronic inflammatory or autoimmune diseases, immunodeficiency diseases, frequent infections, and cancers. Ongoing scientific advances are exploring new avenues in immunology and immune homeostasis maintenance. This chapter introduces the concept of immune homeostasis and its maintenance through different mechanisms.
    Keywords:  Homeostasis; Immune homeostasis; Immunity; Immunohomeostasis; Inflammation
    DOI:  https://doi.org/10.1007/978-1-0716-3754-8_1
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