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

Abstract

Previous studies have implicated T cell production of IL-17 in resistance to T. 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 antigen 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-β. 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 RORγt, and 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.

Poly(inosinic-cytidylic) Acid–Triggered Exacerbation of Experimental Asthma Depends on IL-17A Produced by NK Cells

“…In contrast, lack of IL-23 had no effect on the development of experimental asthma in mice (34). The latter study is in line with our results, whereas IL23p19 (46), and NK cells (47). In our setting, mice with pIC-triggered exacerbation of experimental asthma displayed markedly increased numbers of IL-17-producing NK cells.…”

Absence of Interleukin‐17 Receptor A Signaling Prevents Autoimmune Inflammation of the Joint and Leads to a Th2‐like Phenotype in Collagen‐Induced Arthritis

“…IL-17A and IL-17F are both produced by memory T helper cells, in particular Th17 cells, but also by CD8ϩ, ␥/␦ϩ, and natural killer T cells. Recent studies have demonstrated innate sources of IL-17A, as well as production of IL-17A by tissue-specific cells, such as Paneth cells (14)(15)(16)(17). Both cytokines can be excreted as homodimers or as IL-17A/F heterodimers (18,19).…”

Natural killer (NK) and NK-like cells at mucosal epithelia: Mediators of anti-microbial defense and maintenance of tissue integrity

“…In the absence of cNK cells, impaired priming of CD4 + and CD8 + T cells was observed [50]. Recently, cNK cells have also been identified as a major source of IL-17 during T. gondii infection, a cytokine that confers resistance to this pathogen [51]. In contrast to what has been seen for C. rodentium, IL-22 has pathogenic roles during T. gondii infection, causing destruction of intestinal tissue integrity [52,53].…”