Fig. 3. Effector and Treg cell responses to pathogenic and commensal bacteria.

(A). Effector response to gut bacteria. Under homeostatic conditions, gut resident effector T cells (red) mediate sub-clinical immune response toward commensal bacteria (blue), limiting lamina propria invasion. This subclinical response may also provide protection against pathogenic bacteria (red). During infection, invasive pathogens promote a robust effector T-cell response, leading to their eventual clearance. Simultaneous presentation of commensal antigens during this inflammation can lead to the expansion of commensal-specific effector T cells. Sustained inflammation may lead to feed-forward loop (right) where commensal-T cells alone can maintain inflammation and promote immune response toward additional commensal bacteria and, eventually, overt colitis. (B). Regulatory response to gut bacteria. Under homeostatic conditions, commensal bacteria (orange) drive peripheral conversion of naïve T cells to a regulatory phenotype via the action of tolerogenic dendritic cells (DCs) (green). Pathogens (red) may be able to subvert this process to prevent their elimination by effector cells, potentially leading to the sustained inflammation described in (A). Pathogens that gain access to tolerogenic DCs may lead to generation of Treg rather than effector T cells. Pathogens that share epitopes (yellow star) with commensal bacteria may be protected by commensal-specific regulatory responses.