E-Poster with pre-recorded video presentation Lorne Infection and Immunity 2021

T follicular helper (Tfh)-germinal centre (GC) B cell response is required for sterile immunity during enteric helminth infection (#240)

Aidil Zaini 1 , Kim L Good-Jacobson 1 , Colby Zaph 1
  1. Biomedicine Discovery Institute (BDI), Monash University, Clayton, VIC, Australia

CD4 T follicular helper (Tfh) cells are an important component of germinal centres (GCs), whose overarching goal is to produce an effective humoral immunity. However, the protective roles for Tfh‑GC response during helminth infections remain controversial and poorly understood. Here, we demonstrate that diminished Tfh-GC B cell response is associated with chronic infection of the helminth parasite Trichuris muris (Tm). We show that a high-dose (HD) of parasite eggs in mice that leads to a Th2 cell‑biased acute infection and  worm clearance, results in a significant increase in Tfh and GC B cells, which is typified by the selection of parasite-specific IgG1 class switching. In contrast, a low-dose (LD) infection that results in a Th1 cell-biased chronic infection fails to induce a potent Tfh-GC response. Using the reporter mouse, we further demonstrate that IL-4-producing Th2 cell response predominantly occurs during the first stages of infection and are likely to initially mediate worm expulsion. Conversely, a potent Tfh-GC response is prominent during the last stages of worm expulsion. Strikingly, blockade of Tfh-GC interactions via anti-CD40L treatment during HD infection promotes chronic infection, suggesting Tfh and GC B cells are enablers of complete worm clearance and are thus required for sterile immunity. Overall, these data provide cellular and kinetics insights into the roles of Tfh-GC response during helminth infection and identify a potent Tfh-GC response as a protective component of the type 2 immunity to intestinal helminths.