Th2-dependent STAT6-regulated genes in intestinal epithelial cells mediate larval trapping during secondary Heligmosomoides polygyrus bakeri infection

Westermann S, Schubart C, Dietschmann A, Castiglione K, Radtke D, Vöhringer D (2023)

Publication Type: Journal article

Publication year: 2023

Journal

PLoS Pathogens Public Library of Science

Book Volume: 19

Pages Range: e1011296-

Journal Issue: 4

DOI: 10.1371/journal.ppat.1011296

Abstract

Gastrointestinal helminths are a major health threat worldwide. Alternatively activated macrophages (AAMs) have been shown to contribute to host protection during secondary helminth infections. AAMs express effector molecules that depend on activation of the IL-4- or IL-13-induced transcription factor signal transducer and activator of transcription 6 (STAT6). However, the specific role of STAT6-regulated genes like Arginase-1 (Arg1) from AAMs or STAT6-regulated genes in other cell types for host protection remains unclear. To address this point, we generated mice expressing STAT6 only in macrophages (Mac-STAT6 mouse). In the model of Heligmosomoides polygyrus bakeri (Hpb) infection, Mac-STAT6 mice could not trap larvae in the submucosa of the small intestine after secondary infection. Further, mice lacking Arg1 in hematopoietic and endothelial cells were still protected from secondary Hpb infection. On the other hand, specific deletion of IL-4/IL-13 in T cells blunted AAM polarization, activation of intestinal epithelial cells (IECs) and protective immunity. Deletion of IL-4Rα on IEC also caused loss of larval trapping while AAM polarization remained intact. These results show that Th2-dependent and STAT6-regulated genes in IECs are required and AAMs are not sufficient for protection against secondary Hpb infection by mechanisms that remain to be investigated.

Authors with CRIS profile

Stefanie Westermann Professur für Infektionsabwehr und Toleranz Christoph Schubart Professur für Infektionsabwehr und Toleranz Daniel Radtke Department of Infection Biology David Vöhringer Professur für Infektionsabwehr und Toleranz

Involved external institutions

Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie (Hans-Knöll-Institut (HKI)) / Leibniz Institute for Natural Product Research and Infection Biology DE Germany (DE)

How to cite

APA:

Westermann, S., Schubart, C., Dietschmann, A., Castiglione, K., Radtke, D., & Vöhringer, D. (2023). Th2-dependent STAT6-regulated genes in intestinal epithelial cells mediate larval trapping during secondary Heligmosomoides polygyrus bakeri infection. PLoS Pathogens, 19(4), e1011296-. https://doi.org/10.1371/journal.ppat.1011296

MLA:

Westermann, Stefanie, et al. "Th2-dependent STAT6-regulated genes in intestinal epithelial cells mediate larval trapping during secondary Heligmosomoides polygyrus bakeri infection." PLoS Pathogens 19.4 (2023): e1011296-.

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