Multidimensional regulatory mechanisms of chicken immunity: focus on viral infection, intestinal microbiota and heat stress

Chickens are a vital dietary protein source globally, yet their immune function is increasingly compromised by interconnected challenges including breed specific genetic heterogeneity, viral infections, intestinal microbial dysbiosis, and environmental stressors—all of which hinder sustainable poultry production. The chicken immune system, anchored by central immune organs (bursa of Fabricius, thymus) and peripheral immune organs (spleen, lymph nodes), relies on the coordinated interplay of innate and adaptive immunity to fend off exogenous pathogens. However, the holistic regulatory networks linking genetic background, pathogenic pressure, microbial communities, and environmental cues in shaping chicken immunity remain incompletely resolved. Immune related gene polymorphisms (e.g., MHC-B, TLR4) underpin interbreed differences in immune response magnitude and specificity, while viral pathogens such as Newcastle Disease Virus (NDV) and infectious bursal disease virus (IBDV) disrupt T/B lymphocyte dynamics, alter the expression of immune regulatory microRNAs (miR-155, miR-21) and pro−/anti-inflammatory cytokines (IL-1β, IFN- γ ), and thereby perturb immune homeostasis. The intestinal microbiota, a key mediator of immune function, interacts with intestinal epithelial cells via metabolites (e.g., short-chain fatty acids, bile acids) or modulates the gut immune microenvironment through microbial transplantation, yet the specific targets of core functional taxa and their metabolites in chicken intestinal immunity along with comparative divergences from mammalian systems remain poorly defined. Environmental stressors, particularly heat stress, perturb amino acid metabolism, induce reactive oxygen species accumulation, and disrupt immune cell homeostasis, with synergistic immunosuppressive effects when combined with high density farming and nutritional deficiency. This review synthesizes chicken immune regulation by integrating genetic variation, viral pathogens, intestinal microbiota, and environmental stressors, and defines key regulatory pathways from a host-microbe-environment perspective.