In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 19, No. 4 ( 2023-4-5), p. e1011296-
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.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1011296
DOI:
10.1371/journal.ppat.1011296.g001
DOI:
10.1371/journal.ppat.1011296.g002
DOI:
10.1371/journal.ppat.1011296.g003
DOI:
10.1371/journal.ppat.1011296.g004
DOI:
10.1371/journal.ppat.1011296.g005
DOI:
10.1371/journal.ppat.1011296.g006
DOI:
10.1371/journal.ppat.1011296.s001
DOI:
10.1371/journal.ppat.1011296.s002
DOI:
10.1371/journal.ppat.1011296.s003
DOI:
10.1371/journal.ppat.1011296.s004
DOI:
10.1371/journal.ppat.1011296.s005
DOI:
10.1371/journal.ppat.1011296.s006
DOI:
10.1371/journal.ppat.1011296.s007
DOI:
10.1371/journal.ppat.1011296.s008
DOI:
10.1371/journal.ppat.1011296.s009
DOI:
10.1371/journal.ppat.1011296.s010
DOI:
10.1371/journal.ppat.1011296.s011
DOI:
10.1371/journal.ppat.1011296.r001
DOI:
10.1371/journal.ppat.1011296.r002
DOI:
10.1371/journal.ppat.1011296.r003
DOI:
10.1371/journal.ppat.1011296.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2205412-1
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