Host-Pathogen Interactions in Enteric Infections

Enteric infections arise when pathogenic microorganisms breach the intestinal mucosal barrier and subvert host defences, leading to inflammation, diarrhoea and systemic complications. Key determinants of outcome include the integrity of the epithelial layer, the composition and metabolic activity of the gut microbiota, and the orchestration of innate and adaptive immune responses. Pathogens such as Citrobacter rodentium, enterohaemorrhagic Escherichia coli and Salmonella spp. deploy virulence factors to adhere to and efface epithelial cells, manipulate host metabolism and evade antimicrobial peptides. In turn, the host mounts multilayered defences: secretion of mucus and antimicrobial peptides by goblet and Paneth cells, production of cytokines such as interleukin-22 to reinforce barrier function, recruitment of neutrophils and macrophages for phagocytosis, and activation of T helper subsets to sustain long-term immunity. The resident microbiota contributes to colonisation resistance by competing for nutrients, modulating bile acid and short-chain fatty acid pools, and signalling through microbial metabolites. Recent advances reveal dynamic cross-talk between the liver and intestine via bile remodelling, metabolic checkpoints in T cells that govern cytokine synthesis, and dose-dependent bottlenecks determined by microbial competition. A detailed understanding of these interactions underpins strategies for host-directed therapies, probiotic or dietary interventions and novel vaccines to prevent and treat enteric disease on a global scale.

Research from Nature Portfolio

Recent studies have identified a discrete subset of absorptive colonocytes that present major histocompatibility complex class II and sustain interleukin-22 signalling from pathogen-specific T cells, thereby localising immune protection to sites of enteric invasion. Global metabolomic profiling has uncovered infection-induced remodelling of the bile metabolome, with elevated levels of host-derived itaconate and other dicarboxylates that reshape the gut microbiota and enhance resistance to Vibrio cholerae. Quantitative dose-response analyses using barcoded populations of C. rodentium demonstrate that the resident microbiota establishes a powerful colonisation bottleneck, limiting founder populations in a dose-dependent manner and preserving microbial diversity to defend against pathogen overgrowth.

Research from all publishers

Emerging work has elucidated a Th17 cell-intrinsic glutathione–mitochondrial axis that is essential for optimal interleukin-22 translation and intestinal defence during enteric infection; disruption of antioxidant pathways in T cells impairs mitochondrial function, reduces cytokine output and exacerbates mucosal damage. Separately, the pH-sensing receptor GPR65 expressed by intestinal epithelial cells has been shown to regulate antimicrobial peptide production via STAT3 phosphorylation, maintaining homeostatic barrier integrity and restraining inflammation in inflammatory bowel disease models. These findings underscore the importance of redox balance and epithelial sensory networks in coordinating mucosal immunity and microbial control.

Host-Pathogen Interactions in Enteric Infections publication trend

The graph below shows the total number of articles in host-pathogen interactions in enteric infections across all publications each year (not limited to Nature Index journals).

Technical terms

Interleukin-22 (IL-22): A cytokine produced by Th17 cells and innate lymphoid cells that promotes epithelial cell proliferation, antimicrobial peptide secretion and barrier repair.

Th17 cells: A subset of CD4+ T helper lymphocytes that produce IL-17 and IL-22 and play a key role in mucosal immunity against extracellular pathogens.

Microbiota: The community of commensal and mutualistic microorganisms in the gut that contributes to colonisation resistance and immune modulation.

Mucosal barrier: The combination of epithelial cells, mucus layers and antimicrobial peptides that prevents pathogen translocation and maintains intestinal homeostasis.

Colonisation resistance: The phenomenon whereby resident microbiota inhibit pathogen establishment through competition for nutrients, direct antagonism or immune priming.

Itaconate: A host-derived dicarboxylate metabolite produced during infection that influences microbial growth, immune signalling and bile composition.

References

1. Distal colonocytes targeted by C. rodentium recruit T-cell help for barrier defence. Nature (2024).
2. Enteric bacterial infection stimulates remodelling of bile metabolites to promote intestinal homeostasis. Nature Microbiology (2024).
3. Quantitative dose-response analysis untangles host bottlenecks to enteric infection. Nature Communications (2023).
4. A Th17 cell-intrinsic glutathione/mitochondrial-IL-22 axis protects against intestinal inflammation. Cell Metabolism (2024).
5. Intestinal epithelial pH-sensing receptor GPR65 maintains mucosal homeostasis via regulating antimicrobial defense and restrains gut inflammation in inflammatory bowel disease. Gut Microbes (2023).