Functions of innate immune cells and commensal bacteria in gut homeostasis

Abstract

The intestinal immune system remains unresponsive to beneficial microbes and dietary antigens while activating pro-inflammatory responses against pathogens for host defence. In intestinal mucosa, abnormal activation of innate immunity, which directs adaptive immune responses, causes the onset and/or progression of inflammatory bowel diseases. Thus, innate immunity is finely regulated in the gut. Multiple innate immune cell subsets have been identified in both murine and human intestinal lamina propria. Some innate immune cells play a key role in the maintenance of gut homeostasis by preventing inappropriate adaptive immune responses while others are associated with the pathogenesis of intestinal inflammation through development of Th1 and Th17 cells. In addition, intestinal microbiota and their metabolites contribute to the regulation of innate/adaptive immune responses. Accordingly, perturbation of microbiota composition can trigger intestinal inflammation by driving inappropriate immune responses.

Keywords: adaptive immunity; commensal bacteria; gut homeostasis; inflammatory bowel disease; innate immunity.

Fig. 1.

Murine innate immune subsets in the gut mucosa. (A) CD103⁺ DCs facilitate the differentiation of Foxp3⁺ T_reg cells through the production of retinoic acid and TGF-β. (B) TLR5⁺CD103⁺CD11c⁺ DCs can induce the development of Th1/Th17 cells and IL-22 production in innate lymphoid cells by secreting IL-23 followed by antimicrobial peptide expression in intestinal epithelial cells. (C) CX₃CR1^intermediateCD70⁺CD11b⁺ DCs promote Th17 cell development by producing IL-6 and TGF-β upon ATP stimulus produced by commensal bacteria. (D) CX₃CR1^highM_reg cells can prevent intestinal inflammation by inhibiting effector T cell proliferation. (E) Macrophages suppress production of pro-inflammatory cytokines by myeloid cells due to IL-10 production.

Fig. 2.

Human innate immune subsets in the gut mucosa. (A) CD103⁺SIRPα^high DCs can induce Foxp3⁺ T_reg cells. (B) CD103⁺SIRPα^high DCs and CD103⁺SIRPα^- DCs initiate Th 17 cell development. (C) CD14⁺CD163^low cells induce Th17 differentiation by expression of IL-6, IL-23p19, TNF-α and IL-1β via TLR2, TLR4, and TLR5. (D and E) Colitogenic IL-17 and IFN-γ-producing T cells are induced by CD14⁺CD163^low cells and macrophages in the gut mucosa of patients with IBD.

Fig. 3.

Functions of commensal bacteria on the host immunity. (A) SFB mediate the induction of Th1/Foxp3⁺ T_reg cells and development of Th17 cells in Peyer’s Patches and the small intestine, respectively. (B) Clostridium species initiate the development of Foxp3⁺ T_reg cells in the colon. (C) Bacteroides fragilis-derived polysaccharide A (PSA) contribute to induction of Foxp3⁺ T_reg cells. (D) Micronutrients produced by commensal bacteria including SCFAs and Vitamin 9 participate in maintenance of Foxp3⁺ T_reg cells in the gut.