Segmented filamentous bacteria take the stage

Abstract

Commensal bacteria are crucial for maturation and function of the mucosal immune system. However, the mechanisms of these interactions are poorly understood. In addition, the role of the composition of the microbiota and the importance of individual species in this community in stimulating different types of immunity are major unanswered questions. We recently showed that the balance between two major effector T cell populations in the intestine, IL-17(+) Th17 cells and Foxp3(+) Tregs, requires signals from commensal bacteria and is dependent on the composition of the intestinal microbiota. Comparison of microbiota from Th17 cell-deficient and Th17 cell-sufficient mice identified segmented filamentous bacteria (SFB) as capable of specifically inducing Th17 cells in the gut. SFB represent the first example of a commensal species that can skew the mucosal effector T cell balance and thus affect the immune fitness of the individual.

Figure 1. Segmented filamentous bacteria (SFB) in the terminal ileum of an 8-week old Taconic B6 mouse

SFB (green) are members of the commensal microbiota that colonize wildtype mice at the time of weaning. SFB are endemic for the terminal ileum where they form stable interactions with the villous epithelium (pink). SFB form long filaments that often span the length of several villi. When present, SFB specifically induce the differentiation of effector Th17 cells in the lamina propria. Scanning electron micrograph taken by Alice Liang, NYU and Doug Wei, Carl Zeiss Inc.; artificial coloring by Eric Roth, NYU.

Figure 2. The composition of intestinal microbiota participates in the regulation of immune homeostasis

(Left panel) Signals from different components of the microbiota (different color arrows) regulate different branches of the mucosal T cell response in the lamina propria (corresponding color immune cells). (Right panel) Changes in the composition of commensal bacteria, e.g. introduction of segmented filamentous bacteria (SFB), shift the immune homeostasis in a different direction, in this case increase in the signals mediating induction of Th17 cells (green arrows). This changes the immunological fitness of the individual. In the case of SFB, the increased production of Th17 cell effector cytokines, e.g. IL-17 and IL-22, and the consecutive increase in antimicrobial peptide production from epithelial cells (blue circles) augments the ability of the host to fight off intestinal infections. At the same time, this increase in pro-inflammatory cytokines may render the host more susceptible to chronic autoimmune inflammation. In this way, differences in the repertoire of commensal bacteria between individuals of the same species may account for differences in the nature and robustness of their response in the face of similar environmental challenges.