title: Interleukin 1 enhances vaccine-induced antifungal T-helper 17 cells and resistance against Blastomyces dermatitidis infection.
abstract: Vaccine-induced T-helper 17 (Th17) cells are necessary and sufficient to protect against fungal infection. Although live fungal vaccines are efficient in driving protective Th17 responses and immunity, attenuated fungi may not be safe for human use. Heat-inactivated formulations and subunit vaccines are safer but less potent and require adjuvant to increase their efficacy. Here, we show that interleukin 1 (IL-1) enhances the capacity of weak vaccines to induce protection against lethal Blastomyces dermatitidis infection in mice and is far more effective than lipopolysaccharide. While IL-1 enhanced expansion and differentiation of fungus-specific T cells by direct action on those cells, cooperation with non-T cells expressing IL-1R1 was necessary to maximize protection. Mechanistically, IL-17 receptor signaling was required for the enhanced protection induced by IL-1. Thus, IL-1 enhances the efficacy of safe but inefficient vaccines against systemic fungal infection in part by increasing the expansion of CD4(+) T cells, allowing their entry into the lungs, and inducing their differentiation to protective Th17 cells.
authors.affiliation: Department of Pediatrics, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics, Madison, WI 53706, USA. mwuethri@wisc.edu
authors.forename: Marcel
authors.initials: M
authors.lastname: Wüthrich
authors.forename: Vanessa
authors.initials: V
authors.lastname: LeBert
authors.forename: Kevin
authors.initials: K
authors.lastname: Galles
authors.forename: Jane
authors.initials: J
authors.lastname: Hu-Li
authors.forename: Shlomo Z
authors.initials: SZ
authors.lastname: Ben-Sasson
authors.forename: William E
authors.initials: WE
authors.lastname: Paul
authors.forename: Bruce S
authors.initials: BS
authors.lastname: Klein
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D001758:Blastomyces / Q000276:immunology*; D001759:Blastomycosis / Q000276:immunology / Q000401:mortality / Q000517:prevention & control; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D005657:Fungal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007375:Interleukin-1 / Q000008:administration & dosage*; D008168:Lung / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016019:Survival Analysis; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D005657:Fungal Vaccines; D007375:Interleukin-1
keywords: IL-1; T-cell priming; adjuvant; fungi; vaccine immunity