bims-bac4me Biomed News
on Microbiome and trained immunity
Issue of 2023‒12‒31
eleven papers selected by
Chun-Chi Chang, University Hospital Zurich

  1. Front Microbiol. 2023 ;14 1295215
      The role of the microbiome in asthma is highlighted, considering its influence on immune responses and its connection to alterations in asthmatic patients. In this context, we review the variables influencing asthma phenotypes from a microbiome perspective and provide insights into the microbiome's role in asthma pathogenesis. Previous cohort studies in patients with asthma have shown that the presence of genera such as Bifidobacterium, Lactobacillus, Faecalibacterium, and Bacteroides in the gut microbiome has been associated with protection against the disease. While, the presence of other genera such as Haemophilus, Streptococcus, Staphylococcus, and Moraxella in the respiratory microbiome has been implicated in asthma pathogenesis, indicating a potential link between microbial dysbiosis and the development of asthma. Furthermore, respiratory infections have been demonstrated to impact the composition of the upper respiratory tract microbiota, increasing susceptibility to bacterial diseases and potentially triggering asthma exacerbations. By understanding the interplay between the microbiome and asthma, valuable insights into disease mechanisms can be gained, potentially leading to the development of novel therapeutic approaches.
    Keywords:  asthma; asthma phenotypes; diversity; environmental factors; exacerbations; gut-lung axis; microbiota
  2. Front Cell Infect Microbiol. 2023 ;13 1295063
      Polymicrobial infections include various microorganisms, often necessitating different treatment methods than a monomicrobial infection. Scientists have been puzzled by the complex interactions within these communities for generations. The presence of specific microorganisms warrants a chronic infection and impacts crucial factors such as virulence and antibiotic susceptibility. Game theory is valuable for scenarios involving multiple decision-makers, but its relevance to polymicrobial infections is limited. Eco-evolutionary dynamics introduce causation for multiple proteomic interactions like metabolic syntropy and niche segregation. The review culminates both these giants to form evolutionary dynamics (ED). There is a significant amount of literature on inter-bacterial interactions that remain unsynchronised. Such raw data can only be moulded by analysing the ED involved. The review culminates the inter-bacterial interactions in multiple clinically relevant polymicrobial infections like chronic wounds, CAUTI, otitis media and dental carries. The data is further moulded with ED to analyse the niche colonisation of two notoriously competitive bacteria: S.aureus and P.aeruginosa. The review attempts to develop a future trajectory for polymicrobial research by following recent innovative strategies incorporating ED to curb polymicrobial infections.
    Keywords:  eco-evolutionary dynamics; ecology; game theory; microbial interaction; quorum sensing
  3. Arch Physiol Biochem. 2023 Dec 25. 1-17
      INTRODUCTION: Since the oral cavity is the gateway to the gut, oral microbes likely hold the potential to influence metabolic disease by affecting the gut microbiota.METHOD: A thorough review of literature has been performed to link the alterations in oral microbiota with chronic metabolic disease by influencing the gut microbiota.
    RESULT: A strong correlation exists between abnormalities in oral microbiota and several systemic disorders, such as cardiovascular disease, diabetes, and obesity, which likely initially manifest as oral diseases. Ensuring adequate oral hygiene practices and cultivating diverse oral microflora are crucial for the preservation of general well-being. Oral bacteria have the ability to establish and endure in the gastrointestinal tract, leading to the development of prolonged inflammation and activation of the immune system. Oral microbe-associated prophylactic strategies could be beneficial in mitigating metabolic diseases.
    CONCLUSION: Oral microbiota can have a profound impact on the gut microbiota and influence the pathogenesis of metabolic diseases.
    Keywords:  Oral microbiota; diabetes; gut microbiota; inflammation; metabolic disease; obesity
  4. Immunol Lett. 2023 Dec 22. pii: S0165-2478(23)00204-3. [Epub ahead of print]
      Immunometabolism has been unveiled in the last decade to play a major role in controlling macrophage metabolism and inflammation. There has been a constant effort to understand the immunomodulating properties of regulated metabolites during inflammation with the aim of controlling and re-wiring aberrant macrophages in inflammatory diseases. M-CSF and GM-CSF-differentiated macrophages play a key role in mounting successful innate immune responses. When a resolution phase is not achieved however, GM-CSF macrophages contribute substantially more towards an adverse inflammatory milieu than M-CSF macrophages, consequently driving disease progression. Whether there are specific immunometabolites that determine the homeostatic or inflammatory nature of M-CSF and GM-CSF-differentiated macrophages is still unknown. As such, we performed metabolomics analysis on LPS and IL-4-stimulated M-CSF and GM-CSF-differentiated human macrophages to identify differentially accumulating metabolites. Adenine was distinguished as a metabolite significantly higher in M-CSF-differentiated macrophages after both LPS or IL-4 stimulation. Human macrophages treated with adenine before LPS stimulation showed a reduction in inflammatory gene expression, cytokine secretion and surface marker expression. Adenine caused macrophages to become more quiescent by lowering glycolysis and OXPHOS which resulted in reduced ATP production. Moreover, typical metabolite changes seen during LPS-induced macrophage metabolic reprogramming were absent in the presence of adenine. Phosphorylation of metabolic signaling proteins AMPK, p38 MAPK and AKT were not responsible for the suppressed metabolic activity of adenine-treated macrophages. Altogether, in this study we highlight the immunomodulating capacity of adenine in human macrophages and its function in driving cellular quiescence.
    Keywords:  Adenine; GM-CSF; Immunometabolism; Inflammation; M-CSF; Macrophage
  5. Immunology. 2023 Dec 26.
      Thymic stromal lymphopoietin (TSLP) is a primarily epithelial-derived cytokine that drives type 2 allergic immune responses. Early life viral respiratory infections elicit high TSLP production, which leads to the development of type 2 inflammation and airway hyperreactivity. The goal of this study was to examine in vivo and in vitro the human airway epithelial responses leading to high TSLP production during viral respiratory infections in early infancy. A total of 129 infants (<1-24 m, median age 10 m) with severe viral respiratory infections were enrolled for in vivo (n = 113), and in vitro studies (n = 16). Infants were classified as 'high TSLP' or 'low TSLP' for values above or below the 50th percentile. High versus low TSLP groups were compared in terms of type I-III IFN responses and production of chemokines promoting antiviral (CXCL10), neutrophilic (CXCL1, CXCL5, CXCL8), and type 2 responses (CCL11, CCL17, CCL22). Human infant airway epithelial cell (AEC) cultures were used to define the transcriptomic (RNAseq) profile leading to high versus low TSLP responses in vitro in the absence (baseline) or presence (stimulated) of a viral mimic (poly I:C). Infants in the high TSLP group had greater in vivo type III IFN airway production (median type III IFN in high TSLP 183.2 pg/mL vs. 63.4 pg/mL in low TSLP group, p = 0.007) and increased in vitro type I-III IFN AEC responses after stimulation with a viral mimic (poly I:C). At baseline, our RNAseq data showed that infants in the high TSLP group had significant upregulation of IFN signature genes (e.g., IFIT2, IFI6, MX1) and pro-inflammatory chemokine genes before stimulation. Infants in the high TSLP group also showed a baseline AEC pro-inflammatory state characterized by increased production of all the chemokines assayed (e.g., CXCL10, CXCL8). High TSLP responses in the human infant airways are associated with pre-activated airway epithelial IFN antiviral immunity and increased baseline AEC production of pro-inflammatory chemokines. These findings present a new paradigm underlying the production of TSLP in the human infant airway epithelium following early life viral exposure and shed light on the long-term impact of viral respiratory illnesses during early infancy and beyond childhood.
    Keywords:  TSLP; airway; epithelium; paediatrics; viral bronchiolitis; virus
  6. WIREs Mech Dis. 2023 Dec 26. e1639
      Fungi are the cause of more than a billion infections in humans every year, although their interactions with the host are still neglected compared to bacteria. Major systemic fungal infections are very unusual in the healthy population, due to the long history of coevolution with the human host. Humans are routinely exposed to environmental fungi and can host a commensal mycobiota, which is increasingly considered as a key player in health and disease. Here, we review the current knowledge on host-fungi coevolution and the factors that regulate their interaction. On one hand, fungi have learned to survive and inhabit the host organisms as a natural ecosystem, on the other hand, the host immune system finely tunes the response toward fungi. In turn, recognition of fungi as commensals or pathogens regulates the host immune balance in health and disease. In the human gut ecosystem, yeasts provide a fingerprint of the transient microbiota. Their status as passengers or colonizers is related to the integrity of the gut barrier and the risk of multiple disorders. Thus, the study of this less known component of the microbiota could unravel the rules of the transition from passengers to colonizers and invaders, as well as their dependence on the innate component of the host's immune response. This article is categorized under: Infectious Diseases > Environmental Factors Immune System Diseases > Environmental Factors Infectious Diseases > Molecular and Cellular Physiology.
    Keywords:  fungal evolution; host immunity; host-fungi interaction; mycobiota; trained immunity
  7. Acta Biomater. 2023 Dec 21. pii: S1742-7061(23)00742-0. [Epub ahead of print]
      The threat of infection during implant placement surgery remains a considerable burden for millions of patients worldwide. To combat this threat, clinicians employ a range of anti-infective strategies and practices. One of the most common interventions is the use of prophylactic antibiotic treatment during implant placement surgery. However, these practices can be detrimental by promoting the resilience of biofilm-forming bacteria and enabling them to persist throughout treatment and re-emerge later, causing a life-threatening infection. Thus, it is of the utmost importance to elucidate the events occurring during the initial stages of bacterial surface attachment and determine whether any biological processes may be targeted to improve surgical outcomes. Using gene expression analysis, we identified a cellular mechanism of S. aureus which modifies its cell surface charge following attachment to a medical grade titanium surface. We determined the upregulation of two systems involved in the D-alanylation of teichoic acids and the lysylation of phosphatidylglycerol. We supported these molecular findings by utilizing synchrotron-sourced attenuated total reflection Fourier-transform infrared microspectroscopy to analyze the biomolecular properties of the S. aureus cell surface following attachment. As a direct consequence, S. aureus quickly becomes substantially more tolerant to the positively charged vancomycin, but not the negatively charged cefazolin. The present study can assist clinicians in rationally selecting the most potent antibiotic in prophylaxis treatments. Furthermore, it highlights a cellular process that could potentially be targeted by novel technologies and strategies to improve the outcome of antibiotic prophylaxis during implant placement surgery. STATEMENT OF SIGNIFICANCE: The antibiotic tolerance of bacteria in biofilm is a well-established phenomenon. However, the physiological adaptations employed by Staphylococcus aureus to increase its antibiotic tolerance during the early stages of surface attachment are poorly understood. Using multiple techniques, including gene expression analysis and synchrotron-sourced Fourier-transform infrared microspectroscopy, we generated insights into the physiological response of S. aureus following attachment to a medical grade titanium surface. We showed that this phenotypic transition enables S. aureus to better tolerate the positively charged vancomycin, but not the negatively charged cefazolin. These findings shed light on the antibiotic tolerance mechanisms employed by S. aureus to survive prophylactically administered antibiotics and can help clinicians to protect patients from infections.
    Keywords:  adhesion; biofilm; biomaterials; implant infection; teichoic acids; vancomycin
  8. Cell Rep. 2023 Dec 22. pii: S2211-1247(23)01531-0. [Epub ahead of print]43(1): 113519
      The critical role of the intestinal microbiota in human health and disease is well recognized. Nevertheless, there are still large gaps in our understanding of the functions and mechanisms encoded in the genomes of most members of the gut microbiota. Genome-scale libraries of transposon mutants are a powerful tool to help us address this gap. Recent advances in barcoded transposon mutagenesis have dramatically lowered the cost of mutant fitness determination in hundreds of in vitro and in vivo experimental conditions. In an accompanying review, we discuss recent advances and caveats for the construction of pooled and arrayed barcoded transposon mutant libraries in human gut commensals. In this review, we discuss how these libraries can be used across a wide range of applications, the technical aspects involved, and expectations for such screens.
    Keywords:  CP: Microbiology; chemical genomics; genotype-phenotype mapping; gut microbiota; host-microbe interactions; transposon mutagenesis
  9. Bio Protoc. 2023 Dec 20. 13(24): e4903
      Clearance of dying cells, named efferocytosis, is a pivotal function of professional phagocytes that impedes the accumulation of cell debris. Efferocytosis can be experimentally assessed by differentially tagging the target cells and professional phagocytes and analyzing by cell imaging or flow cytometry. Here, we describe an assay to evaluate the uptake of apoptotic cells (ACs) by human macrophages in vitro by labeling the different cells with commercially available dyes and analysis by flow cytometry. We detail the methods to prepare and label human macrophages and apoptotic lymphocytes and the in vitro approach to determine AC uptake. This protocol is based on previously published literature and allows for in vitro modeling of the efficiency of AC engulfment during continual efferocytosis process. Also, it can be modified to evaluate the clearance of different cell types by diverse professional phagocytes.
    Keywords:  Apoptotic cells; Efferocytosis; Flow cytometry; PBMC-derived macrophages; THP-1-derived macrophage
  10. Front Cell Infect Microbiol. 2023 ;13 1324611
      Background: In the fight against tuberculosis, besides chemotherapy, the regulation of oxidative stress (OS) has also aroused people's interest in host-oriented therapy. However, there is limited research on the genes involved in reactive oxygen species (ROS) production and clearance in macrophages infected with Mycobacterium tuberculosis (MTB). This study analyzes and explores this to provide a basis for exploring new targets for antituberculosis treatments.Methods: We established a macrophage model infected with MTB, counted intracellular bacteria, and determined the ROS produced using flow cytometry. We conducted ribonucleic acid sequencing, screened differentially expressed genes through transcriptomic methods, and validated the expression of them through reverse transcription-quantitative polymerase chain reaction.
    Results: The ROS of macrophages increased with intracellular bacteria at 4 h after infection with MTB and reached its peak at 48 h, surpassing the uninfected macrophages (p < 0.05). A total of 1,613 differentially expressed genes were identified after infection with MTB, of which 458 were associated with ROS, with over 50% involved in the response of organelles and biological processes to stimuli. We analyzed and identified six genes. After macrophage infection with MTB, the expression of CAMK2B increased, whereas the expression of CYBB decreased (p < 0.05). The expression of GPX3 and SOD2 increased, whereas the expression of CAT decreased (p < 0.05).
    Conclusion: The ROS-related differentially expressed genes between MTB infected and uninfected macrophages may be related to some organelles and involved in various biological processes, molecular functions, and signaling pathways. Among them, CAMK2B, GPX3, and SOD2 may be related to ROS.
    Keywords:  Mycobacterium tuberculosis; genes; macrophages; oxidative stress; transcriptome