title: IL-33 Enhances Host Tolerance to Candida albicans Kidney Infections through Induction of IL-13 Production by CD4+ T Cells.
abstract: Susceptibility to systemic Candida albicans infection is determined by immune resistance, as well as by the ability to control Candida-induced immunopathologies. We showed previously that exogenous IL-33 can increase resistance to peritoneal C. albicans infection by regulating multiple steps of the neutrophil anti-Candida response. In this study, using a mouse model of systemic candidiasis, we observed that IL-33 administration limited fungal burden and inflammation and increased survival. In kidneys, IL-33 seemed to directly act on neutrophils and CD4(+) T cells: IL-33 administration enhanced fungal clearance by increasing neutrophil phagocytic activity without which Candida proliferation was uncontrollable. In contrast, IL-33 stimulated CD4(+) T cells to produce IL-13, which, in turn, drove the polarization of macrophages toward the M2 type. Furthermore, the absence of IL-13 abolished IL-33-mediated polarization of M2 macrophages and renal functional recovery. In addition, IL-33 and IL-13 acted synergistically to increase M2 macrophage polarization and its phagocytic activity. Overall, this study identifies IL-33 as a cytokine that is able to induce resistance and tolerance and suggests that targeting resistance and tolerance simultaneously with therapeutic IL-33 may benefit patients with systemic candidiasis.
authors.affiliation: School of Biological Sciences, University of Ulsan, Ulsan 680-749, Republic of Korea;
authors.forename: Vuvi G
authors.initials: VG
authors.lastname: Tran
authors.affiliation: Biomedical Research Center, Ulsan University Hospital, School of Medicine, University of Ulsan, Ulsan 682-714, Republic of Korea; and.
authors.forename: Hye J
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Biomedical Research Center, Ulsan University Hospital, School of Medicine, University of Ulsan, Ulsan 682-714, Republic of Korea; and.
authors.forename: Juyang
authors.initials: J
authors.lastname: Kim
authors.affiliation: School of Biological Sciences, University of Ulsan, Ulsan 680-749, Republic of Korea;
authors.forename: Sang W
authors.initials: SW
authors.lastname: Kang
authors.affiliation: School of Biological Sciences, University of Ulsan, Ulsan 680-749, Republic of Korea;
authors.forename: U J
authors.initials: UJ
authors.lastname: Moon
authors.affiliation: Biomedical Research Center, Ulsan University Hospital, School of Medicine, University of Ulsan, Ulsan 682-714, Republic of Korea; and Department of Surgery, Ulsan University Hospital, School of Medicine, University of Ulsan, Ulsan 682-714, Republic of Korea bkwon@mail.ulsan.ac.kr hrcho@uuh.ulsan.kr.
authors.forename: Hong R
authors.initials: HR
authors.lastname: Cho
authors.affiliation: School of Biological Sciences, University of Ulsan, Ulsan 680-749, Republic of Korea; bkwon@mail.ulsan.ac.kr hrcho@uuh.ulsan.kr.
authors.forename: Byungsuk
authors.identifier: http://orcid.org/0000-0001-8575-0115
authors.initials: B
authors.lastname: Kwon
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007108:Immune Tolerance / Q000276:immunology*; D018793:Interleukin-13 / Q000096:biosynthesis / Q000276:immunology*; D000067596:Interleukin-33; D007378:Interleukins / Q000276:immunology*; D007674:Kidney Diseases / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C506535:Il33 protein, mouse; D018793:Interleukin-13; D000067596:Interleukin-33; D007378:Interleukins