**4. Gut-resident macrophages and microbial dysbiosis in IBD**

Intestinal epithelium mononuclear phagocytes (MPs) have been designated as the 'sensors' and 'responders' to the intestinal environment by virtue of their location and function. They are represented by heterogeneous dendritic cell (DC) and macrophage subsets which are vital for the induction of immune response and regulation of inflammation [34]. Mononuclear phagocytes keep the intestinal inflammation in check either through direct regulation of microbiota or through the release of local anti-inflammatory molecules. Mononuclear phagocytes expressing the fractalkine receptor CX3CR1 and displaying a macrophage phenotype, play a key role in the uptake and sampling of bacterial and fungal antigens from the intestinal lumen [35–39].

Gut microbiota has a crucial role in maintaining tolerogenic function i.e., immunological tolerance of intestinal macrophages and bacterial dysbiosis has strongly been associated with intestinal inflammation and IBD [40–42]. Intestinal epithelium-adhering bacteria can interact with CX3CR1 MPs to regulate the immune balance in health and diseases. The enrichment of adherent-invasive *Escherichia coli* in ileal mucosa has been described in active Crohn's disease [43, 44]. This bacterium stimulates the production of IL-10 by CX3CR MPs and suppresses the Th17 immune responses [44, 45]. *Klebsiella* species derived from the oral cavity have been found to inhabit the intestine of IBD patients and induce severe colitis by the activation of Th1 proinflammatory immune response [46].

Koscsó *et al.* [47] performed extensive phenotypical, transcriptional, and functional analyses of intestinal inflammatory MPs in Salmonella colitis model. CX3CR1+ MPs were identified as the predominating inflammatory cell type and were further divided into monocyte-derived Nos2+ CX3CR1lo, lymph migratory Ccr7<sup>+</sup> CX3CR1int and mucosa resident Cxcl13+ CX3CR1hi subsets. An increase in MPs in the inflamed bowel was found to be directly related to the increase in CX3CR1lo, CX3CR1int and CX3CR1hi macrophage populations and thus, have an apparent role in the induction of pathogen-specific mucosal IgA response [34, 47]. These studies suggest that CX3CR1 MPs are crucial in maintaining immune homeostatic conditions and controlling intestinal disease development.
