IL-6 Promotes NK Cell Production of IL-17 during Toxoplasmosis

Previous studies have implicated T cell production of IL-17 in resistance to Toxoplasma gondii as well as the development of immune-mediated pathology during this infection. Analysis of C57BL/6 and C57BL/6 RAG(-/-) mice challenged with T. gondii-identified NK cells as a major innate source of IL-17....

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Published in:The Journal of immunology (1950) 2010-02, Vol.184 (4), p.1776-1783
Main Authors: Passos, Sara T, Silver, Jonathan S, O'Hara, Aisling C, Sehy, David, Stumhofer, Jason S, Hunter, Christopher A
Format: Article
Language:English
Subjects:
Acute Disease
Animals
Cell Differentiation - genetics
Cell Differentiation - immunology
Cells, Cultured
Homeodomain Proteins - genetics
Immunity, Innate - genetics
Interleukin-17 - biosynthesis
Interleukin-6 - physiology
Killer Cells, Natural - immunology
Killer Cells, Natural - parasitology
Killer Cells, Natural - pathology
Killer Cells, Natural - secretion
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Toxoplasma - immunology
Toxoplasmosis, Animal - immunology
Toxoplasmosis, Animal - metabolism
Toxoplasmosis, Animal - pathology
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Summary:Previous studies have implicated T cell production of IL-17 in resistance to Toxoplasma gondii as well as the development of immune-mediated pathology during this infection. Analysis of C57BL/6 and C57BL/6 RAG(-/-) mice challenged with T. gondii-identified NK cells as a major innate source of IL-17. The ability of soluble Toxoplasma Ag to stimulate NK cells to produce IL-17 was dependent on the presence of accessory cells and the production of IL-6, IL-23, and TGF-beta. In contrast, these events were inhibited by IL-2, IL-15, and IL-27. Given that IL-6 was one of the most potent enhancers of NK cell production of IL-17, further studies revealed that only a subset of NK cells expressed both chains of the IL-6R, IL-6 upregulated expression of the Th17-associated transcription factor RORgammat, and that IL-6(-/-) mice challenged with T. gondii had a major defect in NK cell production of IL-17. Together, these data indicate that many of the same cytokines that regulate Th17 cells are part of a conserved pathway that also control innate production of IL-17 and identify a major role for IL-6 in the regulation of NK cell responses.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.0901843