Microbes, immunoregulation, and the gut

Abstract

Two distinct, but rapidly converging, areas of research (the hygiene hypothesis and the study of probiotic/prebiotic effects) have emphasised the need to understand, and ultimately to manipulate, our physiological interactions with commensal flora, and with other transient but harmless organisms from the environment that affect immunoregulatory circuits. The story began with allergic disorders but now inflammatory bowel disease is increasingly involved.

Figure 1

A diagram of the hypothesised modes of action of “old friends” and immunoregulatory probiotics. The “old friends”, which have been present throughout mammalian evolutionary history, are recognised as harmless by the innate immune system and so cause antigen presenting cells (APC) to mature into regulatory APC (APC_reg) that drive regulatory T cell (T_reg). Some of these T_reg will recognise the “old friends” themselves and so provide continuous background bystander regulation. However, APC_reg will also process and present epitopes from self, allergens, and gut contents, and so drive specific immunoregulation. These mechanisms can be silenced in the presence of appropriate danger signals. In the absence of “old friends”, both specific and bystander regulation will be defective. IL-10, interleukin 10; TGF-β, transforming growth factor β; TLR2, toll-like receptor 2.