The Gut Microbiota Crosstalk with the Host Immune System in Health and Disease

Abstract

The gut microbiota both regulates and stimulates the immune system to impact many aspects of immunity, including the response to infection and the development of autoimmunity. This is driven in large part by the unique environment of the mucosal tissues, where host cells reside in close proximity to the microbiota. The mammalian host incorporates barriers and mechanisms to control interactions with the microbiota, and significant cross-talk occurs between the microbiota constituents and the innate and adaptive elements of the host immune system. While great strides have been made in defining how the microbiota affects the host, particularly in regard to intestinal immunity and function, more remains to be determined regarding how the gut microbiota impacts gut-distal diseases. Here, we demonstrate that the gut commensal Segmented Filamentous Bacteria (SFB) is protective in a mouse model of pneumonia in immunodeficient hosts. During the resolution phase of disease, lung neutrophils are decreased, and undergo a phenotypic switch from inflammatory to pro-resolution, mediated in part by downregulation of the anti-efferocytosis transmembrane glycoprotein CD47. We also show that the purinergic receptor P2X7 is potentially required in a T cell-intrinsic manner to control the development of disease in autoimmune arthritis. T cell immunoglobulin and ITIM-containing (TIGIT) levels are upregulated on P2rx7-/- T follicular helper (Tfh) cells, which may contribute to deregulation of cell death and expansion of the Tfh population. This work contributes to our understanding of how the gut microbiota impacts gut-distal infection and autoimmunity through changes in innate and adaptive immune cells.