In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 16, No. 12 ( 2020-12-22), p. e1009121-
Abstract:
Parasitic helminths are sensed by the immune system via tissue-derived alarmins that promote the initiation of the appropriate type 2 immune responses. Here we establish the nuclear alarmin cytokine IL-33 as a non-redundant trigger of specifically IL-9-driven and mast cell-mediated immunity to the intestinal parasite Strongyloides ratti . Blockade of endogenous IL-33 using a helminth-derived IL-33 inhibitor elevated intestinal parasite burdens in the context of reduced mast cell activation while stabilization of endogenous IL-33 or application of recombinant IL-33 reciprocally reduced intestinal parasite burdens and increased mast cell activation. Using gene-deficient mice, we show that application of IL-33 triggered rapid mast cell-mediated expulsion of parasites directly in the intestine, independent of the adaptive immune system, basophils, eosinophils or Gr-1 + cells but dependent on functional IL-9 receptor and innate lymphoid cells (ILC). Thereby we connect the described axis of IL-33-mediated ILC2 expansion to the rapid initiation of IL-9-mediated and mast cell-driven intestinal anti-helminth immunity.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1009121
DOI:
10.1371/journal.ppat.1009121.g001
DOI:
10.1371/journal.ppat.1009121.g002
DOI:
10.1371/journal.ppat.1009121.g003
DOI:
10.1371/journal.ppat.1009121.g004
DOI:
10.1371/journal.ppat.1009121.g005
DOI:
10.1371/journal.ppat.1009121.g006
DOI:
10.1371/journal.ppat.1009121.s001
DOI:
10.1371/journal.ppat.1009121.s002
DOI:
10.1371/journal.ppat.1009121.s003
DOI:
10.1371/journal.ppat.1009121.s004
DOI:
10.1371/journal.ppat.1009121.s005
DOI:
10.1371/journal.ppat.1009121.s006
DOI:
10.1371/journal.ppat.1009121.s007
DOI:
10.1371/journal.ppat.1009121.s008
DOI:
10.1371/journal.ppat.1009121.s009
DOI:
10.1371/journal.ppat.1009121.s010
DOI:
10.1371/journal.ppat.1009121.s011
DOI:
10.1371/journal.ppat.1009121.s012
DOI:
10.1371/journal.ppat.1009121.s013
DOI:
10.1371/journal.ppat.1009121.r001
DOI:
10.1371/journal.ppat.1009121.r002
DOI:
10.1371/journal.ppat.1009121.r003
DOI:
10.1371/journal.ppat.1009121.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2020
detail.hit.zdb_id:
2205412-1
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