Peripheral education of the immune system by the colonic microbiota

Abstract

There is growing interest in understanding the effects of host-microbial interactions on host physiologic processes. Much of the work in this arena is logically focused on the interaction at mucosal surfaces as this is a primary site of interaction. However, there is ample evidence to suggest that the effects of the microbiota have a much farther reach including the systemic immune system. While there are some similarities to effects at mucosal surfaces (i.e. reduced numbers of adaptive immune cells, diminished innate responses), there are some important differences that we highlight such as the response to immunogens and bacterial antigens. We propose that understanding the details of how specific components of the microbiota influence the systemic immune system likely will have significant impact on our understanding the pathophysiology of a variety of autoimmune diseases.

Keywords: APC; CCP; Commensal bacteria; DC; GPI; Host–microbial interactions; IBD; LN; MLN; Microbiome; PAD; PSA; RA; SCFA; SFB; SPF; Systemic immunity; TNBS; antigen presenting cell; cyclic citrullinated peptide; dendritic cell; glucose-6-phosphate isomerase; inflammatory bowel disease; lymph node; mesenteric lymph node; peptidylarginine deiminase; polysaccharide A; rheumatoid arthritis; segmented filamentous bacteria; short-chain fatty acid; specific-pathogen free; trinitrobenzene sulphonic acid.

Figure 1. Model of microbial influences on systemic immune development

Germ-free mice have hypoplastic secondary immune organs with little B cell differentiation and Th2 skewed responses. Upon colonization, the architecture of secondary immune organs is restored. T and B cell responses normalize to represent a more diverse repertoire, which is dependent upon microbial interactions with innate antigen presenting cells (APC).