Interactions between the microbiota and the immune system

Abstract

The large numbers of microorganisms that inhabit mammalian body surfaces have a highly coevolved relationship with the immune system. Although many of these microbes carry out functions that are critical for host physiology, they nevertheless pose the threat of breach with ensuing pathologies. The mammalian immune system plays an essential role in maintaining homeostasis with resident microbial communities, thus ensuring that the mutualistic nature of the host-microbial relationship is maintained. At the same time, resident bacteria profoundly shape mammalian immunity. Here, we review advances in our understanding of the interactions between resident microbes and the immune system and the implications of these findings for human health.

Figures

Figure 1. Looking inside-out: immune system control of the microbiota

(A) Several immune effectors function together to stratify luminal microbes and to minimize bacterial-epithelial contact. This includes the mucus layer produced by goblet cells, epithelial antibacterial proteins, and immunoglobulin A secreted by lamina propria plasma cells. (B) The zones of containment of the intestinal microbiota by the immune system are illustrated by dashed lines. The red dotted line represents the lower intestinal epithelial cell layer, above which secreted mucus, peptides, proteins and antibodies combine to stratify the intestinal microbiota and limit access to the epithelium. Some microbes are sampled by intestinal dendritic cells (DC), shown as green cells carrying brown bacilli. The loaded DC traffic to the mesenteric lymph nodes through the intestinal lymphatics (yellow), but do not penetrate further into the body. This compartmentalizes live bacteria and induction of immune responses to the mucosal immune system, shown by the blue dashed line. There is recirculation of induced B cells (blue) and some T cell subsets through the lymphatics and the bloodstream to home back to mucosal sites, where B cells differentiate into IgA-secreting plasma cells. The spleen and liver are capable of filtering any live microbes that penetrate the systemic bloodstream – these are eliminated by the biocidal activity of splenic and hepatic phagocytes. The stomach and upper intestine have very low levels of microbial colonization as a result of acid and bile secretion in the stomach and duodenum and constant intestinal motility: this creates the necessary microbial exclusion zone for the host to have the first priority to digest dietary nutrients.

Figure 2. Looking outside-in: how microbiota shape host immunity

Timelines of development of lymphopoietic tissues, secondary lymphoid structures and leukocyte populations. Events dependent on colonisation with a microbiota are shown in red text and with red arrows. Immune system development and maintenance that is independent of microbiota colonisation is shown in black. En = embryo age (days), birth = E19-21, weaning at approximately postnatal day 20, CSR=class switch recombination.