title: IL-23 protection against Plasmodium berghei infection in mice is partially dependent on IL-17 from macrophages.
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.
authors.affiliation: Department of Parasitology, Graduate School of Medicine, Gunma University, Maebashi, Japan.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Ishida
authors.forename: Takashi
authors.initials: T
authors.lastname: Imai
authors.forename: Kazutomo
authors.initials: K
authors.lastname: Suzue
authors.forename: Makoto
authors.initials: M
authors.lastname: Hirai
authors.forename: Tomoyo
authors.initials: T
authors.lastname: Taniguchi
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshimura
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Hiroko
authors.initials: H
authors.lastname: Okada
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Suzuki
authors.forename: Chikako
authors.initials: C
authors.lastname: Shimokawa
authors.forename: Hajime
authors.initials: H
authors.lastname: Hisaeda
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D053760:Interleukin-23 Subunit p19 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D008288:Malaria / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D018512:Parasitemia / Q000235:genetics; D010962:Plasmodium berghei / Q000276:immunology*; D013154:Spleen / Q000473:pathology
chemical_list: D018932:Chemokine CCL2; D020381:Interleukin-17; D053760:Interleukin-23 Subunit p19
keywords: IL-17; IL-23; Macrophage; Malaria; Plasmodium berghei