Critical Role for the Microbiota in CX3CR1+ Intestinal Mononuclear Phagocyte Regulation of Intestinal T Cell Responses

Abstract

The intestinal barrier is vulnerable to damage by microbiota-induced inflammation that is normally restrained through mechanisms promoting homeostasis. Such disruptions contribute to autoimmune and inflammatory diseases including inflammatory bowel disease. We identified a regulatory loop whereby, in the presence of the normal microbiota, intestinal antigen-presenting cells (APCs) expressing the chemokine receptor CXCR1 reduced expansion of intestinal microbe-specific T helper 1 (Th1) cells and promoted generation of regulatory T cells responsive to food antigens and the microbiota itself. We identified that disruption of the microbiota resulted in CXCR1 APC-dependent inflammatory Th1 cell responses with increased pathology after pathogen infection. Colonization with microbes that can adhere to the epithelium was able to compensate for intestinal microbiota loss, indicating that although microbial interactions with the epithelium can be pathogenic, they can also activate homeostatic regulatory mechanisms. Our results identify a cellular mechanism by which the microbiota limits intestinal inflammation and promotes tissue homeostasis.

Response to Fungal Dysbiosis by Gut-Resident CX3CR1+ Mononuclear Phagocytes Aggravates Allergic Airway Disease

“…Gut-resident CX3CR1 + MNPs play a critical role in regulation of intestinal immune response to bacteria and fungi under homeostatic and dysbiotic conditions (Diehl et al, 2013; Kim et al, 2018; Leonardi et al, 2018; Panea et al, 2015). Although fluconazole treatment contributed to increases of CD4 + T cell frequencies in the lung of HDM-immunized mice, we did not observe changes in CX3CR1 + MNPs frequencies in the lung of those mice (Figure 4A).…”

The impact of exercise training and resveratrol supplementation on gut microbiota composition in high-fat diet fed mice

“…; Kim et al. ). The potential interaction between the gut microbiota and resveratrol is not yet well documented, but due to it's low bioavailability it is predicted that resveratrol reaches the colonic region of the intestine unabsorbed and unchanged, and therefore it may be subjected to enzymatic degradation by the gut microbiota (Etxeberria et al.…”

Adherent‐invasive Escherichia coli (AIEC): Cause or consequence of inflammation, dysbiosis, and rupture of cellular joints in patients with IBD?

“…The genomics of the AIEC strain is enriched with several genes, including propanediol ( pduC ) and long polar fimbriae ( lpfA ) (Dogan et al, ; Miquel et al, ; Sobieszczanska et al, ). These are related to the ability to use fucose, a component of intestinal mucin, capable of inducing the response of intestinal T cells in the lamina propria, invading epithelial cells, translocating across epithelial junctions microfold cells (M‐cells), surviving and replicating in macrophages (Chassaing et al, ; Chassaing, Etienne‐Mesmin, Bonnet, & Darfeuille‐Michaud, ; Dogan et al, ; Kim et al, ; Viladomiu et al, ).…”

“…These are related to the ability to use fucose, a component of intestinal mucin, capable of inducing the response of intestinal T cells in the lamina propria, invading epithelial cells, translocating across epithelial junctions microfold cells (M-cells), surviving and replicating in macrophages(Chassaing et al, 2011;Chassaing, Etienne-Mesmin, Bonnet, & Darfeuille-Michaud, 2013;Dogan et al, 2014;Kim et al, 2018;Viladomiu et al, 2017).…”