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

Aidil Zaini (Leading Author), Lennard Dalit, Amania A. Sheikh, Yan Zhang, Daniel Thiele, Jessica Runting, Grace Rodrigues, Judy Ng, Michael Bramhall, Sebastian Scheer, Lauren Hailes, Joanna R. Groom, Kim L. Good-Jacobson (Leading Author), Colby Zaph (Leading Author)

Research output: Contribution to journalArticleResearchpeer-review

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 interferon-γ. In contrast, interleukin-4-producing Tfh cells dominate responses to an acute, resolving infection. Heightened expression and increased chromatin accessibility of T helper (Th)1- and Th2 cell-associated genes are 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 T. muris infection.

Original languageEnglish
Pages (from-to)642-657
Number of pages16
JournalMucosal Immunology
Volume16
Issue number5
DOIs
Publication statusPublished - Oct 2023

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