The avian respiratory microenvironment-immune nexus: A three-dimensional regulation model from local homeostasis to...

The avian respiratory tract is a major portal of entry for respiratory pathogens, and the dynamic interactions between the mucosal immune system and resident microbial communities constitute an important component of local defense. Although these interactions are increasingly recognized, substantial knowledge gaps remain regarding the molecular mediators of the gut-lung axis, the interplay between the microbiota and tissue-resident memory T (TRM) cells, and the mechanisms that maintain local homeostasis. This review synthesizes multidisciplinary advances in avian respiratory immunology and microbiome research. We distinguish direct evidence obtained in avian species from mechanisms inferred from mammalian studies and identify the latter as hypotheses requiring validation in birds. We discuss a putative regulatory axis linking dominant respiratory and intestinal microbial taxa, microbial metabolites such as short-chain fatty acids (SCFAs) and pyrroloquinoline quinone (PQQ), and mucosal immune effectors including secretory immunoglobulin A (sIgA) and interferon lambda 3 (IFN-λ3). We further examine the proposed pathways through which dysbiosis may contribute to the progression from local barrier disruption to systemic disease. Considering avian anatomical and immunological characteristics, including nasal-associated lymphoid tissue (NALT) and the absence of conventional draining lymph nodes in chickens and turkeys, we propose a host-microbiota-environment framework for organizing the determinants of respiratory homeostasis and disease susceptibility. Furthermore, we review the application of high-throughput sequencing and gene-editing technologies to target discovery and discuss the potential translation of microecological interventions into poultry production. Collectively, this review provides a conceptual basis for investigating avian respiratory microecology and supports the evaluation of microbiota-directed approaches as potential complements to vaccination, biosecurity, environmental management, and antimicrobial stewardship.