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.