bims-bac4me 2024-12-29 papers

bims-bac4me

Biomed News

on Microbiome and trained immunity

Issue of 2024–12–29
nineteen papers selected by
Chun-Chi Chang, Universitäts Spital Zürich

Trained Immunity Enhances Host Resistance to Infection in Aged Mice.
GM-CSF engages multiple signaling pathways to enhance pro-inflammatory cytokine responses in human monocytes during Legionella infection.
Hematopoietic stem cell a reservoir of innate immune memory.
Regulated Cell Death of Alveolar Macrophages in Acute Lung Inflammation: Current Knowledge and Perspectives.
Muramyl dipeptide potentiates Staphylococcus aureus lipoteichoic acid-induced nitric oxide production via TLR2/NOD2/PAFR signaling pathways.
Transcription factor-mediated reprogramming to antigen-presenting cells.
Evidence of sex differences in ozone-induced oxysterol and cytokine levels in differentiated human nasal epithelial cells.
Exogenous acetate attenuates inflammatory responses through HIF-1α-dependent glycolysis regulation in macrophage.
Reciprocal regulation between bacterial secretion systems and host metabolism: Enhancing bacterial intracellular survival capability.
Bletilla striata polysaccharide-mediated trained immunity drives the hematopoietic progenitors' expansion and myelopoiesis.
Maternal probiotic exposure enhances CD8 T cell protective neonatal immunity and modulates offspring metabolome to control influenza virus infection.
[Protective effect of Streptococcus salivarius K12 against Mycoplasma pneumoniae infection in mice].
Development of a Caco-2-based intestinal mucosal model to study intestinal barrier properties and bacteria-mucus interactions.
How microbial growth adapts to temperature shifts.
The di-leucine motif in the host defense peptide LL-37 is essential for initiation of autophagy in human macrophages.
The role of cGAS-STING signaling pathway in ferroptosis.
Listeria monocytogenes use multiple mechanisms to disseminate from the intestinal lamina propria to the mesenteric lymph nodes.
Microbial metabolism of host-derived antioxidants.
The impact of glucose metabolism on inflammatory processes in sepsis-induced acute lung injury.

J Leukoc Biol. 2024 Dec 26. pii: qiae259. [Epub ahead of print]

Trained Immunity Enhances Host Resistance to Infection in Aged Mice.

Dan Hao, Katherine R Caja, Margaret A McBride, Allison M Owen, Julia K Bohannon, Antonio Hernandez, Sabah Ali, Sujata Dalal, David L Williams, Edward R Sherwood.

  Aging significantly increases the incidence and severity of infections, with individuals aged 65 and above accounting for 65% of sepsis cases. Innate immune training, known as "trained immunity" or "innate immune memory", has emerged as a potential strategy to enhance infection resistance by modulating the aging immune system. We investigated the impact of β-glucan-induced trained immunity on aged mice (18-20 months old) compared to young adult mice (10-12 weeks old). Our findings showed that β-glucan equally augmented the host resistance to infection in both young and aged mice. This enhancement was characterized by augmented bacterial clearance, enhanced leukocyte recruitment and decreased cytokine production in response to Pseudomonas aeruginosa infection. Furthermore, young and aged trained macrophages displayed heightened metabolic capacity and improved antimicrobial functions, including enhanced phagocytosis and respiratory burst. RNA-seq analysis showed a distinctive gene expression pattern induced by trained immunity in macrophages characterized by activation of pathways regulating inflammation and the host response to infection and suppression of pathways regulating cell division, which was consistently observed in both young and aged groups. As compared to macrophages from young mice, aged macrophages showed increased activation of gene ontology pathways regulating angiogenesis, connective tissue deposition and wound healing. Our results indicate that immune training can be effectively induced in aging mice, providing valuable insights into potential strategies for enhancing infection resistance in the elderly.

Keywords:   β-glucan; immunometabolism; infection; trained immunity

DOI:  https://doi.org/10.1093/jleuko/qiae259
bioRxiv. 2024 Dec 10. pii: 2024.12.05.627084. [Epub ahead of print]

GM-CSF engages multiple signaling pathways to enhance pro-inflammatory cytokine responses in human monocytes during Legionella infection.

Víctor R Vázquez Marrero, Madison Dresler, Mikel D Haggadone, Allyson Lu, Sunny Shin.

The proinflammatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) is required for host defense against a wide range of pathogens. We previously found that GM-CSF enhances inflammatory cytokine production in murine monocytes and is required for in vivo control of the intracellular bacterial pathogen Legionella pneumophila . It is unclear whether GM-CSF similarly augments cytokine production in human monocytes during bacterial infection. Here, we find that GM-CSF enhances inflammatory cytokine expression in Legionella- infected human monocytes by engaging multiple signaling pathways. Legionella - and TLR-dependent NF-𝜅B signaling is a prerequisite signal for GM-CSF to promote cytokine expression. Then, GM-CSF-driven JAK2/STAT5 signaling is required to augment cytokine expression in Legionella -infected human monocytes. We also found a role for PI-3K/Akt/mTORC1 signaling in GM-CSF-dependent upregulation of cytokine expression. Finally, glycolysis and amino acid metabolism are also critical for GM-CSF to boost cytokine gene expression in human monocytes during infection. Our findings show that GM-CSF-mediated enhancement of cytokine expression in infected human monocytes is regulated by multiple signaling pathways, thereby allowing the host to fine tune antibacterial immunity.

DOI: https://doi.org/10.1101/2024.12.05.627084
Front Immunol. 2024 ;15 1491729

Hematopoietic stem cell a reservoir of innate immune memory.

Lucas Ruffinatto, Yann Groult, Johanna Iacono, Sandrine Sarrazin, Bérengère de Laval.

  Hematopoietic stem cells (HSCs) are a rare, long-lived and multipotent population that give rise to majority of blood cells and some tissue-resident immune cells. There is growing evidence that inflammatory stimuli can trigger persistent reprogramming in HSCs that enhances or inhibits the cellular functions of these HSCs and their progeny in response to subsequent infections. This newly discovered property makes HSCs a reservoir for innate immune memory. The molecular mechanisms underlying innate immune memory in HSCs are similar to those observed in innate immune cells, although their full elucidation is still pending. In this review, we examine the current state of knowledge on how an inflammatory response leads to reprogramming of HSCs. Understanding the full spectrum of consequences of reshaping early hematopoiesis is critical for assessing the potential benefits and risks under physiological and pathological conditions.

Keywords:  emergency hematopoiesis; epigenetic; hematopoietic stem and progenitor cells (HSPCs); inflammation; innate immune memory; metabolism; myelopoiesis

DOI:  https://doi.org/10.3389/fimmu.2024.1491729
J Inflamm Res. 2024 ;17 11419-11436

Regulated Cell Death of Alveolar Macrophages in Acute Lung Inflammation: Current Knowledge and Perspectives.

Siwei Xia, Xiaoyan Gu, Gaojian Wang, Yizhi Zhong, Fengjie Ma, Qinxue Liu, Junran Xie.

  Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a common and serious clinical lung disease characterized by extensive alveolar damage and inflammation leading to impaired gas exchange. Alveolar macrophages (AMs) maintain homeostatic properties and immune defenses in lung tissues. Several studies have reported that AMs are involved in and regulate ALI/ARDS onset and progression via different regulated cell death (RCD) programs, such as pyroptosis, apoptosis, autophagic cell death, and necroptosis. Notably, the effects of RCD in AMs in disease are complex and variable depending on the environment and stimuli. In this review, we provide a comprehensive perspective on how regulated AMs death impacts on ALI/ARDS and assess its potential in new therapeutic development. Additionally, we describe the crosstalk between different RCD types in ALI, and provide new perspectives for the treatment of ALI/ARDS and other severe lung diseases.

Keywords:  acute lung injury; alveolar macrophage; apoptosis; autophagic cell death; necroptosis; pyroptosis

DOI:  https://doi.org/10.2147/JIR.S497775
Front Immunol. 2024 ;15 1451315

Muramyl dipeptide potentiates Staphylococcus aureus lipoteichoic acid-induced nitric oxide production via TLR2/NOD2/PAFR signaling pathways.

Jintaek Im, Jun Ho Jeon, Dongwook Lee, Jeong Woo Park, Woohyung Jun, Suwon Lim, Ok-Jin Park, Cheol-Heui Yun, Seung Hyun Han.

  Lipoteichoic acid (LTA) and peptidoglycan (PGN) are considered as key virulence factors of Staphylococcus aureus, which is a representative sepsis-causing Gram-positive pathogen. However, cooperative effect of S. aureus LTA and PGN on nitric oxide (NO) production is still unclear despite the pivotal roles of NO in initiation and progression of sepsis. We here evaluated the cooperative effects of S. aureus LTA (SaLTA) and muramyl dipeptide (MDP), the minimal structure of PGN, on NO production in both a mouse macrophage-like cell line, RAW 264.7 and mouse bone marrow-derived macrophages (BMMs). Although MDP alone did not affect NO production, MDP potently enhanced SaLTA-induced NO production via the expression of inducible NO synthases. The enhanced NO production was ameliorated in BMMs from TLR2-, CD14-, MyD88-, and NOD2-deficient mice. Moreover, the augmented SaLTA-induced NO production by MDP was attenuated by inhibitors specific for PAFR and MAP kinases. Furthermore, MDP also potently increased SaLTA-induced activities of STAT1, NF-κB, and AP-1 transcription factors, and specific inhibitors for these transcription factors suppressed the elevated NO production. Collectively, these results demonstrated that MDP potentiates SaLTA-induced NO production via TLR2/NOD2/PAFR, MAP kinases signaling axis, resulting in the activation of NF-κB, AP-1 and STAT1 transcription factors.

Keywords:  Staphylococcus aureus; lipoteichoic acid; macrophages; muramyl dipeptide; nitric oxide; peptidoglycan

DOI:  https://doi.org/10.3389/fimmu.2024.1451315
Curr Opin Genet Dev. 2024 Dec 24. pii: S0959-437X(24)00149-7. [Epub ahead of print]90 102300

Transcription factor-mediated reprogramming to antigen-presenting cells.

Ervin Ascic, Carlos-Filipe Pereira.

Antigen-presenting cells (APCs) are a heterogenous group of immune cells composed by dendritic cells (DCs) and macrophages (Mϕ), which are critical for orchestrating immunity against cancer or infections. Several strategies have been explored to generate APC subsets, including enrichment from peripheral blood and differentiation from pluripotent or multipotent cells. During development, the generation of APC subsets is instructed by transcription factors (TFs). Direct cell reprogramming, also known as transdifferentiation, offers an approach to harness combinations of TFs to generate APCs from unrelated somatic cells, including cancer cells. In this review, we summarize the transcriptional specification of DC subsets, highlight transcriptional networks for their generation, and discuss future applications of DC reprogramming in cancer immunotherapy.

DOI: https://doi.org/10.1016/j.gde.2024.102300
Am J Physiol Lung Cell Mol Physiol. 2024 Dec 24.

Evidence of sex differences in ozone-induced oxysterol and cytokine levels in differentiated human nasal epithelial cells.

Dre'Von A Dobson, Alexia Perryman, Erin McNell, Hye-Young H Kim, Ned A Porter, Meghan E Rebuli, Ilona Jaspers.

  Acute exposure to ozone (O3) causes upper and lower airway inflammation. We and others have previously demonstrated that O3 oxidizes lipids, particularly cholesterol, into electrophilic oxysterols, such as secosterol B (SecoB), which can adduct proteins, thus altering cellular signaling pathways. To investigate how O3-derived oxysterols influence cytokine and chemokine release, nasal epithelial cells (HNECs) from healthy donors (N = 18 donors) were exposed to 0.4ppm O3 for 4 hours. Afterward, immune mediators in apical washes and basolateral supernatants were analyzed using ELISAs, while sterol and oxysterol levels were examined using LC-MS. O3 exposure increased SecoB, 7-ketocholesterol (7Keto-Chol), 27-hydroxycholesterol (27OH-Chol), and epoxycholesterols in a sex-dependent manner. Female-derived HNECs had significant increases in SecoB, 27OH-Chol, and β-epoxycholesterol, while male-derived cells showed increases in 7Keto-Chol only. O3 decreased the release of Granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-7 but increased IL-1β, IL-6, IL-8, VEGF, and Eotaxin. Females exhibited O3-induced IL-1β and VEGF increases, while males showed increased Eotaxin and reduced GM-CSF. Basolaterally, O3 exposure decreased GM-CSF and TARC while raising IL-6, IL-13, IL- 1β, IL-8, and TNFα. Females showed higher TNFα and IL-1β, but males did not. Oxysterols correlated differently with cytokines by sex. Females showed positive correlations between oxysterols and pro52 inflammatory cytokines like IL-6 and IL-1β, while males displayed negative correlations with IL-6, IL-8, and TNFα. In conclusion, O3-induced cytokine/chemokine responses and sterol/oxysterol levels in HNECs vary by sex, with donor-specific oxysterols associated with O3-triggered inflammatory mediator release.

Keywords:  cytokines; epithelial cells; oxysterol; ozone; sex differences

DOI:  https://doi.org/10.1152/ajplung.00332.2024
Cell Mol Life Sci. 2024 Dec 27. 82(1): 21

Exogenous acetate attenuates inflammatory responses through HIF-1α-dependent glycolysis regulation in macrophage.

Na Li, Yi Gong, Yalin Zhu, Bo Li, Changli Wang, Zhefan Wang, Jun Wang, Jie Huang, Jinjun Bian, Yan Zhang.

  Cytokine storm is a hallmark for acute systemic inflammatory disease like sepsis. Intrinsic microbiome-derived short-chain fatty acid (SCFAs) like acetate modulates immune cell function and metabolism has been well studied. However, it remains poorly investigated about the effects and the underlying mechanism of exogenous acetate in acute inflammation like sepsis. Here, we observed that serum acetate accumulates in patients undergoing abdominal gastrointestinal surgery and in septic mice. Short exposure to high-dose exogenous acetate protects mice from sepsis by inhibiting glycolysis in macrophages, both in vivo and in vitro. Hypoxia-inducible factor 1 subunit alpha (HIF-1α) stabilization or overexpression reverses the decreased glycolysis and pro-inflammatory cytokine production in macrophages and abrogates acetate's protective effect in septic mice. Meanwhile, we also found acetyl-CoA synthetase-2, but not GPR41 or GPR43, plays a key role in acetate's immunosuppressive effect. Acetate transiently increases acetyl-coenzyme A production, promoting histone acetylation and decreasing acetyl-transfer to NF-κB p65. These findings suggest that short exposure to mM-level acetate inhibits macrophage immune response linked to HIF-1α-dependent glycolysis. Taken together, we demonstrate short-term exposure of exogenous acetate could regulate inflammatory responses through attenuating HIF-1α-dependent glycolysis.

Keywords:  Acetate; Glycolysis; HIF-1alpha; Inflammation; Macrophage

DOI:  https://doi.org/10.1007/s00018-024-05521-8
Microbiol Res. 2024 Dec 16. pii: S0944-5013(24)00426-9. [Epub ahead of print]292 128025

Reciprocal regulation between bacterial secretion systems and host metabolism: Enhancing bacterial intracellular survival capability.

Lina Zhan, Jiongchen Ge, Lin Xia, Ying Zhang.

  Secretion systems are intricate nanomachines present on many bacterial cell membranes that deliver various bacterially-encoded effector proteins into eukaryotic or prokaryotic cells. They are pivotal in bacterial invasion, host colonization, and pathogenesis. After infection, bacteria employ these machines to deliver toxic effectors to the cytoplasm of host cells that disrupt their metabolic balance, such as interfering with glucose metabolism, promoting lipid droplets formation, altering amino acid profiles and mitochondrial morphology, and reducing ROS levels, to ensure bacterial intracellular survival. Furthermore, metabolites within host cells can modulate the expression and/or function of bacterial secretion systems. This review summarizes recent advancements in understanding the impact of bacterial secretion systems on host cell metabolism and the feedback regulation of host metabolites on these machines, providing novel perspectives on host-pathogen interactions and mechanisms of bacterial pathogenesis.

Keywords:  Bacterial secretion systems; Glycolysis; Host metabolism; Lipid droplets; Mitochondria

DOI:  https://doi.org/10.1016/j.micres.2024.128025
Int Immunopharmacol. 2024 Dec 24. pii: S1567-5769(24)02431-7. [Epub ahead of print]146 113909

Bletilla striata polysaccharide-mediated trained immunity drives the hematopoietic progenitors' expansion and myelopoiesis.

Jiangtao Zhang, Chao Zhong, Lanying Chen, Yingying Luo, Le Tang, Jing Yang, Jing Jia, Xinxu Xie, Peng Liu, Jun Yu, Yaru Cui.

  Trained immunity represents a functional state of the innate immune response, characterized by enduring epigenetic reprogramming of innate immune cells. This phenomenon facilitates a sustained and advantageous reaction of myeloid cells to subsequent challenges. Bletilla striata polysaccharide (BSP) is the primary active component of Bletilla striata, mainly consisting of mannose and glucose in its chemical structure. Previous studies have demonstrated BSP's immunomodulatory properties, highlighting its effectiveness in enhancing the immune response. In the present study, we demonstrated that BSP administration induced the trained innate immunity, as evidenced by the BSP-induced generation of mature myeloid cells, especially neutrophils in the peripheral circulation in amouse model of chemotherapy-induced myelosuppression. Furthermore, we showed that BSP-induced trained immunity acts at the level of hematopoietic stem and progenitor cells (HSPCs) and induces the expansion of HSPCs. Mechanistically, our study demonstrated that BSP induced the activation of Notch signaling in HSPCs, and Notch signaling is indispensable for the BSP-mediated generation of trained HSPCs. Collectively, our data demonstrated for the first time that BSP induced trained immunity by regulating theexpansion of the myeloid progenitors. Harnessing trained immunity could be a promising strategy for protection from chemotherapy-induced myelosuppression.

Keywords:  Bletilla striata polysaccharide; Chemotherapy; Hematopoietic stem and progenitor cells; Trained immunity

DOI:  https://doi.org/10.1016/j.intimp.2024.113909
Gut Microbes. 2025 Dec;17(1): 2442526

Maternal probiotic exposure enhances CD8 T cell protective neonatal immunity and modulates offspring metabolome to control influenza virus infection.

Clara Valentin, Patricia Brito Rodrigues, Marko Verce, Sandrine Delbauve, Léa La Palombara, Florine Demaret, Justine Allard, Isabelle Salmon, Patrice D Cani, Arnaud Köhler, Amandine Everard, Véronique Flamand.

  Maternal gut microbiota composition contributes to the status of the neonatal immune system and could influence the early life higher susceptibility to viral respiratory infections. Using a novel protocol of murine maternal probiotic supplementation, we report that perinatal exposure to Lacticaseibacillus rhamnosus (L.rh) or Bifidobacterium animalis subsp. lactis (B.lac) increases the influenza A/PR8 virus (IAV) clearance in neonates. Following either supplementation, type 1 conventional dendritic cells (cDC1) were amplified in the lymph nodes leading to an enhanced IAV antigen-experienced IFN-γ producing effector CD8 T cells in neonates and IAV-specific resident memory CD8 T cells in adulthood. This was compatible with a higher protection of the offspring upon a secondary infection. Interestingly, only mice born to L.rh supplemented mothers further displayed an increased activation of IFN-γ producing virtual memory CD8 T cells and a production of IL-10 by CD4 and CD8 T cells that could explain a better control of the lung damages upon infection. In the offspring and the mothers, no disturbance of the gut microbiota was observed but, as analyzed through an untargeted metabolomic approach, both exposures modified neonatal plasma metabolites. Among them, we further demonstrated that genistein and 3-(3-hydroxyphenyl)propionic acid recapitulate viral clearance or cDC1 activation in neonates exposed to IAV. We conclude that maternal L.rh or B.lac supplementation confers the neonates specific metabolomic modulations with a better CD8 T cell-mediated immune protection against IAV infection.

Keywords:  Bifidobacterium; CD8 T cells; IAV; Lacticaseibacillus rhamnosus; early life; memory response

DOI:  https://doi.org/10.1080/19490976.2024.2442526
Nan Fang Yi Ke Da Xue Xue Bao. 2024 Dec 20. pii: 1673-4254(2024)12-2300-08. [Epub ahead of print]44(12): 2300-2307

[Protective effect of Streptococcus salivarius K12 against Mycoplasma pneumoniae infection in mice].

Xiaoling Su, Daoyong Liao, Chao Li, Li Chen, Jingyun Wang, Tian Gan, Haodang Luo, Ning Wu, Jun He.

   OBJECTIVES: To investigate the protective effect of the probiotic bacterium Streptococcus salivarius K12 (K12) against Mycoplasma pneumoniae (Mp) infection in mice.
METHODS: Forty male BALB/c mice were randomized into normal control group, K12 treatment group, Mp infection group, and K12 pretreatment prior to Mp infection group. The probiotic K12 was administered daily by gavage for 14 days before Mp infection induced by intranasal instillation of Mp. Three days after Mp infection, the mice were euthanized for analysis of bronchoalveolar lavage fluid (BALF) cell counts and serum levels of secretory immunoglobulin A (sIgA), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). RT-qPCR was performed to detect the P1 and community-acquired respiratory distress syndrome ( CARDS ) toxin of Mp in the lung tissues and the mRNA expressions of TNF-α, IL-6, chemokine 1 (CXCL1), matrix metalloproteinase 9 (MMP9), mucin 5ac (MUC5ac), collagen 3a1 (Col3a1), Toll-like receptor 2 (TLR2) and TLR4; the protein expressions of TLR2 and TLR4 in the lung tissue were detected using Western blotting. Pathological changes in the lung tissue and airway remodeling were examined with HE staining and AB/PAS staining.
RESULTS: Compared with the Mp-infected mice with PBS treatment, the infected mice with K12 treatment showed significantly lowered mRNA levels of P1 and CARDS in the lung tissue and reduced white blood cell counts in the BALF (P<0.05). In spite of the absence of significant differences in serum levels of inflammatory factors between the two groups, the mRNA expressions of TNF‑α, IL-6, CXCL1, MMP9, MUC5ac and COL3A1 and the mRNA and protein levels of TLR2 and TLR4 in the lung tissues were significantly lower in K12-treated mice, in which AB/PAS staining showed obviously decreased mucus secretion.
CONCLUSIONS: K12 pretreatment can effectively reduce pulmonary inflammatory responses, improve airway remodeling and alleviate lung injury in Mp-infected mice.

Keywords:  BALB/c mice; Mycoplasma pneumoniae; Mycoplasma pneumoniae infection model; Streptococcus salivarius K12; oral probiotics

DOI:  https://doi.org/10.12122/j.issn.1673-4254.2024.12.05
Gut Microbes. 2025 Dec;17(1): 2434685

Development of a Caco-2-based intestinal mucosal model to study intestinal barrier properties and bacteria-mucus interactions.

Evelien Floor, Jinyi Su, Maitrayee Chatterjee, Elise S Kuipers, Noortje IJssennagger, Faranak Heidari, Laura Giordano, Richard W Wubbolts, Silvia M Mihăilă, Daphne A C Stapels, Yvonne Vercoulen, Karin Strijbis.

  The intestinal mucosal barrier is a dynamic system that allows nutrient uptake, stimulates healthy microbe-host interactions, and prevents invasion by pathogens. The mucosa consists of epithelial cells connected by cellular junctions that regulate the passage of nutrients covered by a mucus layer that plays an important role in host-microbiome interactions. Mimicking the intestinal mucosa for in vitro assays, particularly the generation of a mucus layer, has proven to be challenging. The intestinal cell-line Caco-2 is widely used in academic and industrial laboratories due to its capacity to polarize, form an apical brush border, and reproducibly grow into confluent cell layers in different culture systems. However, under normal culture conditions, Caco-2 cultures lack a mucus layer. Here, we demonstrate for the first time that Caco-2 cultures can form a robust mucus layer when cultured under air-liquid interface (ALI) conditions on Transwell inserts with addition of vasointestinal peptide (VIP) in the basolateral compartment. We demonstrate that unique gene clusters are regulated in response to ALI and VIP single stimuli, but the ALI-VIP combination treatment resulted in a significant upregulation of multiple mucin genes and proteins, including secreted MUC2 and transmembrane mucins MUC13 and MUC17. Expression of tight junction proteins was significantly altered in the ALI-VIP condition, leading to increased permeability to small molecules. Commensal Lactiplantibacillus plantarum bacteria closely associated with the Caco-2 mucus layer and differentially colonized the surface of the ALI cultures. Pathogenic Salmonella enterica were capable of invading beyond the mucus layer and brush border. In conclusion, Caco-2 ALI-VIP cultures provide an accessible and straightforward way to culture an in vitro intestinal mucosal model with improved biomimetic features. This novel in vitro intestinal model can facilitate studies into mucus and epithelial barrier functions and in-depth molecular characterization of pathogenic and commensal microbe-mucus interactions.

Keywords:  ALI; ETEC; Lactiplantibacillus plantarum; MUC2; Mucus; Salmonella enterica serovar Enteritidis; VIP; air–liquid growth; gut-on-a-chip; intestinal mucosa; tight junctions; transwell

DOI:  https://doi.org/10.1080/19490976.2024.2434685
Nat Microbiol. 2024 Dec 23.

How microbial growth adapts to temperature shifts.

DOI: https://doi.org/10.1038/s41564-024-01847-y
Cell Rep. 2024 Dec 20. pii: S2211-1247(24)01382-2. [Epub ahead of print]44(1): 115031

The di-leucine motif in the host defense peptide LL-37 is essential for initiation of autophagy in human macrophages.

Rokeya Sultana Rekha, Avinash Padhi, Nicolai Frengen, Julia Hauenstein, Ákos Végvári, Birgitta Agerberth, Robert Månsson, Guðmundur H Guðmundsson, Peter Bergman.

  The human cathelicidin peptide LL-37 induces autophagy in human macrophages. Different post-translational modifications (PTMs) such as citrullination, acetylation, and formylation impact LL-37, yet their effect on autophagy remains unknown. Thus, we set out to study how the cellular source could impact PTM of LL-37 and subsequent effects on autophagy initiation. Neutrophil-released LL-37 failed to induce autophagy, unlike macrophage-released LL-37. Mass spectrometry analysis revealed modifications on neutrophil-derived LL-37, especially at the N terminus, while macrophage-derived LL-37 remained mostly native. Native LL-37 initiated autophagy, while formylated and acetylated versions did not. Truncated peptides lacking the N-terminal di-leucine motif or substituted with di-alanine did not initiate autophagy. Native LL-37 failed to initiate autophagy in macrophages with genetic inactivation of dipeptidyl peptidase-1. An intact N-terminal di-leucine motif in LL-37 was crucial for autophagy initiation, and modifications abrogated the effects. This pathway presents a novel way to regulate the effects of LL-37 in infection or inflammation.

Keywords:  CP: Immunology; LL-37; Papillon Lefevre syndrome; cathelicidin; dipeptidyl peptidase 1; lysosomal damage; macrophages; post-translational modification

DOI:  https://doi.org/10.1016/j.celrep.2024.115031
J Adv Res. 2024 Dec 20. pii: S2090-1232(24)00606-4. [Epub ahead of print]

The role of cGAS-STING signaling pathway in ferroptosis.

Lina Ding, Ruicheng Zhang, Wenqi Du, Qingling Wang, Dongsheng Pei.

  The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway has been identified as a crucial mechanism in antiviral defense and innate immunity pathway. Ferroptosis, characterized by iron dependence and lipid peroxidation, represents a specialized form of cell death. A burgeoning collection of studies has demonstrated that the cGAS-STING signaling pathway participates in the homeostatic regulation of the organism by modulating ferroptosis-associated enzyme activity or gene expression. Consequently, elucidating the specific roles of the STING signaling pathway and ferroptosis in vivo is vital for targeted disease intervention. This review systematically examines the interactions between the cGAS-STING signaling pathway and ferroptosis, highlighting their influence on disease progression in the contexts of inflammation, injury, and cancerous cell dynamics. Understanding these interactions may provide novel therapeutic strategies. The STING pathway has been implicated in the regulation of various cell death mechanisms, including apoptosis, pyroptosis, necroptosis, autophagy, and ferroptosis. Our focus primarily addresses the role and mechanism of the cGAS-STING signaling pathway and ferroptosis in diseases, limiting discussion of other cell death modalities and precluding a comprehensive overview of the pathway's additional functions.

Keywords:  Cancer; Ferroptosis; Inflammation; Injury; cGAS-STING

DOI:  https://doi.org/10.1016/j.jare.2024.12.028
Microbiol Spectr. 2024 Dec 23. e0259524

Listeria monocytogenes use multiple mechanisms to disseminate from the intestinal lamina propria to the mesenteric lymph nodes.

Joshua S Nowacki, Grant S Jones, Sarah E F D'Orazio.

  Listeria monocytogenes are facultative intracellular bacterial pathogens that cause foodborne disease in humans. The bacteria can use the surface protein InlA to invade intestinal epithelial cells or transcytose across M cells in the gut, but it is not well understood how the bacteria traffic from the underlying lamina propria to the draining mesenteric lymph nodes (MLN). Previous studies indicated that L. monocytogenes associated with both monocytes and dendritic cells in the intestinal lamina propria. We show here that CCR2-/- mice had a significant reduction in Ly6Chi monocytes in the MLN but no change in bacterial burden following foodborne infection; thus, dissemination of L. monocytogenes associated with monocytes is not required for colonization of the MLN. To block CCR7-mediated trafficking of dendritic cells from the lamina propria, we treated mice with anti-VEGFR3 antibody (clone AFL4) prior to and during infection but did not see a change in dendritic numbers in the MLN as had been previously reported with other anti-VEGFR3-specific antibodies. However, increasing the number of circulating dendritic cells by treating mice with rFlt3L resulted in a significant increase in L. monocytogenes in the lymph nodes that drain the small intestine and the spleen. Whole-mount fluorescent microscopy of lymphatic vessels following ligated loop infection revealed both free-floating L. monocytogenes and cell-associated bacteria within lymphatic vessels. Together, these results suggest that L. monocytogenes can use multiple, redundant mechanisms to disseminate from the gut tissue to the MLN.
IMPORTANCE: Consumption of the foodborne bacterial pathogen Listeria monocytogenes results in a wide spectrum of human disease from mild self-limiting gastroenteritis to life-threatening infections of the bloodstream, brain, and placenta. It is not well understood how the bacteria migrate from the intestines to the draining mesenteric lymph nodes, which are thought to serve as the last barrier to prevent systemic infections. Results presented here reveal multiple redundant mechanisms L. monocytogenes can use to disseminate from the ileum or colon to the mesenteric lymph nodes.

Keywords:  facutatively intracellular pathogens; foodborne; gastrointestinal infection; lymph nodes

DOI:  https://doi.org/10.1128/spectrum.02595-24
Curr Opin Chem Biol. 2024 Dec 24. pii: S1367-5931(24)00141-8. [Epub ahead of print]84 102565

Microbial metabolism of host-derived antioxidants.

Zhe Zhou, Stavroula K Hatzios.

  Humans are exposed to a wide variety of small molecules with antioxidant properties that are poorly metabolized by mammalian cells. However, gastrointestinal microbes encode enzymes that convert these redox-active molecules into nutrient sources and electron acceptors to support bacterial growth in the gut. Here, we describe recent studies highlighting how microbial metabolism of host-derived antioxidants modulates interspecies interactions and provide an overview of the interdisciplinary approaches being used to map these metabolic pathways in vivo. Uncovering microbe-driven biotransformations of redox-active small molecules could create new opportunities to improve human health by modulating redox reactions at the host-microbe interface.

Keywords:  Antioxidants; Bacterial metabolism; Gut microbiome; Host–microbe interactions; Metabolomics

DOI:  https://doi.org/10.1016/j.cbpa.2024.102565
Front Immunol. 2024 ;15 1508985

The impact of glucose metabolism on inflammatory processes in sepsis-induced acute lung injury.

Shilei Cheng, Yufei Li, Xiaoliang Sun, Zhirui Liu, Liang Guo, Jueheng Wu, Xiaohan Yang, Sisi Wei, Guanghan Wu, Shilong Xu, Fan Yang, Jianbo Wu.

  Acute lung injury (ALI) is a prevalent and critical complication of sepsis, marked by high incidence and mortality rates, with its pathogenesis still not being fully elucidated. Recent research has revealed a significant correlation between the metabolic reprogramming of glucose and sepsis-associated ALI (S-ALI). Throughout the course of S-ALI, immune cells, including macrophages and dendritic cells, undergo metabolic shifts to accommodate the intricate demands of immune function that emerge as sepsis advances. Indeed, glucose metabolic reprogramming in S-ALI serves as a double-edged sword, fueling inflammatory immune responses in the initial stages and subsequently initiating anti-inflammatory responses as the disease evolves. In this review, we delineate the current research progress concerning the pathogenic mechanisms linked to glucose metabolic reprogramming in S-ALI, with a focus on the pertinent immune cells implicated. We encapsulate the impact of glucose metabolic reprogramming on the onset, progression, and prognosis of S-ALI. Ultimately, by examining key regulatory factors within metabolic intermediates and enzymes, We have identified potential therapeutic targets linked to metabolic reprogramming, striving to tackle the inherent challenges in diagnosing and treating Severe Acute Lung Injury (S-ALI) with greater efficacy.

Keywords:  ALI; glycolysis; immune response; metabolic reprogramming; oxidative phosphorylation (OXPHOS); sepsis

DOI:  https://doi.org/10.3389/fimmu.2024.1508985