Pathogenesis of various pulmonary diseases by tuning immune response: insight from host-microbial crosstalk

Growing research has highlighted the participation of lung microbiota in various pathological processes. Despite its low bacterial biomass compared with other organs, the resident flora of the healthy lung is essential for immune system development, immune tolerance fostering, and defense against foreign substance incursion. The host-microbial crosstalk, typically mediated by microbial metabolites, pattern recognition receptors, and immune cells, exerts bidirectional regulatory effects on the pulmonary immune microenvironment. Specifically, the lung microbiota modulates the activation status or tolerance of mucosal immune cell populations to maintain immune balance; conversely, perturbations to the lung's homeostatic microbiome, arising from dysbiosis, immune dysfunction, or pathogenic invasion, drive lung disease by inciting chronic inflammation and tissue remodeling via direct and immune mediated damage. Although the importance of host-microbial interactions in lung health is well recognized, the mechanisms of the relationship between changes in microbiota composition and immune dysregulation in different diseases have not been fully elucidated. Therefore, we summarize the latest research progress on the involvement of the lung microbiota in pulmonary disease development, focusing on the interaction mechanisms among microorganisms, immune homeostasis, and lung diseases. The aim of this review is to expand our mechanistic understanding of the lung microbiota-mediated regulation of immune cell function. Insights from various disciplines into lung microbiota could pave the way for innovative ideas and technologies aimed at preventing and treating respiratory illnesses.