Heterogeneous Tfh cell populations that develop during enteric helminth infection predict the quality of type 2 protective response

Zaini, A; Dalit, L; Sheikh, AA; Zhang, Y; Thiele, D; Runting, J; Rodrigues, G; Ng, J; Bramhall, M; Scheer, S; Hailes, L; Groom, JR; Good-Jacobson, KL; Zaph, C

Author(s): Zaini, A; Dalit, L; Sheikh, AA; Zhang, Y; Thiele, D; Runting, J; Rodrigues, G; Ng, J; Bramhall, M; Scheer, S; Hailes, L; Groom, JR; Good-Jacobson, KL; Zaph, C;
Details: Publication Year 2023-06-29,Volume 16,Issue #5,Page 642-657
Journal Title: Mucosal Immunology
Abstract: T follicular helper (Tfh) cells are an important component of germinal center (GC)-mediated humoral immunity. Yet, how a chronic type 1 versus protective type 2 helminth infection modulates Tfh-GC responses remains poorly understood. Here, we employ the helminth Trichuris muris model and demonstrate that Tfh cell phenotypes and GC are differentially regulated in acute versus chronic infection. The latter failed to induce Tfh-GC B cell responses, with Tfh cells expressing Τ-bet and IFN-γ. In contrast, IL-4-producing Tfh cells dominate responses to an acute, resolving infection. Heightened expression and increased chromatin accessibility of Th1- and Th2 cell-associated genes is observed in chronic and acute induced Tfh cells, respectively. Blockade of the Th1 cell response by T cell-intrinsic T-bet deletion promoted Tfh cell expansion during chronic infection, pointing to a correlation between a robust Tfh cell response and protective immunity to parasites. Finally, blockade of Tfh-GC interactions impaired type 2 immunity, revealing the critical protective role of GC-dependent Th2-like Tfh cell responses during acute infection. Collectively, these results provide new insights into the protective roles of Tfh-GC responses and identify distinct transcriptional and epigenetic features of Tfh cells that emerge during resolving or chronic Trichuris muris infection.
Publisher: Elsevier
Keywords: T follicular helper cell; germinal center; helminth; host-parasite interaction
Research Division(s): Immunology
PubMed ID: 37392971/
Publisher's Version: https://doi.org/10.1016/j.mucimm.2023.06.007
Open Access at Publisher's Site: https://doi.org/10.1016/j.mucimm.2023.06.007
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-07-12 08:05:01

Last Modified: 2023-12-13 10:19:45