1. IL-23 protection against Plasmodium berghei infection in mice is partially dependent on IL-17 from macrophages.
- Author
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Ishida H, Imai T, Suzue K, Hirai M, Taniguchi T, Yoshimura A, Iwakura Y, Okada H, Suzuki T, Shimokawa C, and Hisaeda H
- Subjects
- Adoptive Transfer, Animals, Cell Movement genetics, Cells, Cultured, Chemokine CCL2 metabolism, Female, Humans, Interleukin-17 genetics, Interleukin-17 immunology, Interleukin-23 Subunit p19 genetics, Interleukin-23 Subunit p19 immunology, Macrophages parasitology, Macrophages pathology, Malaria genetics, Mice, Mice, Inbred C57BL, Mice, Knockout, Models, Animal, Parasitemia genetics, Spleen pathology, Interleukin-17 metabolism, Interleukin-23 Subunit p19 metabolism, Macrophages immunology, Malaria immunology, Plasmodium berghei immunology
- Abstract
Although IL-12 is believed to contribute to protective immune responses, the role played by IL-23 (a member of the IL-12 family) in malaria is elusive. Here, we show that IL-23 is produced during infection with Plasmodium berghei NK65. Mice deficient in IL-23 (p19KO) had higher parasitemia and died earlier than wild-type (WT) controls. Interestingly, p19KO mice had lower numbers of IL-17-producing splenic cells than their WT counterparts. Furthermore, mice deficient in IL-17 (17KO) suffered higher parasitemia than the WT controls, indicating that IL-23-mediated protection is dependent on induction of IL-17 during infection. We found that macrophages were responsible for IL-17 production in response to IL-23. We observed a striking reduction in splenic macrophages in the p19KO and 17KO mice, both of which became highly susceptible to infection. Thus, IL-17 appears to be crucial for maintenance of splenic macrophages. Adoptive transfer of macrophages into macrophage-depleted mice confirmed that macrophage-derived IL-17 is required for macrophage accumulation and parasite eradication in the recipient mice. We also found that IL-17 induces CCL2/7, which recruit macrophages. Our findings reveal a novel protective mechanism whereby IL-23, IL-17, and macrophages reduce the severity of infection with blood-stage malaria parasites., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2013
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