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. 2017 Sep 7;8:1105. doi: 10.3389/fimmu.2017.01105

Figure 1.

Figure 1

Role and regulation of interferon gamma (IFN-γ) during infection with African trypanosomes. Regulation: CD4+ T cells (16, 18, 21–24), CD8+ T cells (18–20), NK cells (18), and NKT cells (18) produce IFN-γ during infection with African trypanosomes. African trypanosomes activate mononuclear phagocytes to secrete IL-12 through TLR9 and MyD88 signaling (25). IL-12 stimulates CD4+ T cells to produce IFN-γ via activation of STAT4 signaling (26), whereas IL-27 inhibits CD4+ T cells to secrete IFN-γ (24). Interleukin 10, mainly synthesized by CD4+ (22, 23, 27) and myeloid cells (28), inhibits IFN-γ production through downregulation of the secretion of IL-12 by direct modulation of mononuclear phagocytes (2). Protective role: IFN-γ enhances Kupffer cell phagocytosis of trypanosomes circulating in the bloodstream (12, 13). IFN-γ also promotes M1 myeloid cells to produce TNF-α and nitric oxide, which mediate parasite lysis (16, 29–31). Detrimental effects: excessive secretions of IFN-γ lead to liver pathology (12, 24, 26, 32) and activation of erythrophagocytic myeloid cells, resulting in anemia (18).