Abstract
Here we identified B cells as a major source of rapid, innate-like production of interleukin 17 (IL-17) in vivo in response to infection with Trypanosoma cruzi. IL-17(+) B cells had a plasmablast phenotype, outnumbered cells of the TH17 subset of helper T cells and were required for an optimal response to this pathogen. With both mouse and human primary B cells, we found that exposure to parasite-derived trans-sialidase in vitro was sufficient to trigger modification of the cell-surface mucin CD45, which led to signaling dependent on the kinase Btk and production of IL-17A or IL-17F via a transcriptional program independent of the transcription factors RORγt and Ahr. Our combined data suggest that the generation of IL-17(+) B cells may be a previously unappreciated feature of innate immune responses required for pathogen control or IL-17-mediated autoimmunity.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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B-Lymphocytes / immunology*
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B-Lymphocytes / parasitology
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Cell Proliferation
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Cells, Cultured
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Chagas Disease / genetics
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Chagas Disease / immunology*
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Glycoproteins / genetics
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Glycoproteins / metabolism*
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Humans
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Interleukin-17 / immunology*
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Lymphocyte Activation
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Neuraminidase / genetics
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Neuraminidase / metabolism*
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Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
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Receptors, Aryl Hydrocarbon / metabolism
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T-Lymphocytes, Helper-Inducer / immunology
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T-Lymphocytes, Helper-Inducer / parasitology
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Th17 Cells / immunology
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Th17 Cells / parasitology
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Transcriptional Activation / immunology
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Trypanosoma cruzi / enzymology*
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Trypanosoma cruzi / immunology*
Substances
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Glycoproteins
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Interleukin-17
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Nuclear Receptor Subfamily 1, Group F, Member 3
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Receptors, Aryl Hydrocarbon
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trans-sialidase
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Neuraminidase