Vaccine-induced protection against 3 systemic mycoses endemic to North America requires Th17 cells in mice

Date
2011-01-04
Authors
Wüthrich, Marcel
Gern, Benjamin
Hung, Chiung-Yu
Ersland, Karen
Rocco, Nicole
Pick-Jacobs, John
Galles, Kevin
Filutowicz, Hanna
Warner, Thomas
Evans, Michael
Journal Title
Journal ISSN
Volume Title
Publisher
American Society for Clinical Investigation
Abstract

Worldwide rates of systemic fungal infections, including three of the major pathogens responsible for such infections in North America (Coccidioides posadasii, Histoplasma capsulatum, and Blastomyces dermatitidis), have soared recently, spurring interest in developing vaccines. The development of Th1 cells is believed to be crucial for protective immunity against pathogenic fungi, whereas the role of Th17 cells is vigorously debated. In models of primary fungal infection, some studies have shown that Th17 cells mediate resistance, while others have shown that they promote disease pathology. Here, we have shown that Th1 immunity is dispensable and that fungus-specific Th17 cells are sufficient for vaccine-induced protection against lethal pulmonary infection with B. dermatitidis in mice. Further, vaccine-induced Th17 cells were necessary and sufficient to protect against the three major systemic mycoses in North America. Mechanistically, Th17 cells engendered protection by recruiting and activating neutrophils and macrophages to the alveolar space, while the induction of Th17 cells and acquisition of vaccine immunity unexpectedly required the adapter molecule Myd88 but not the fungal pathogen recognition receptor Dectin-1. These data suggest that human vaccines against systemic fungal infections should be designed to induce Th17 cells if they are to be effective.

Description
Keywords
Coccidioides posadasii, Histoplasma capsulatum, Blastomyces dermatitidis
Citation
Wüthrich, M., Gern, B., Hung, C. Y., Ersland, K., Rocco, N., Pick-Jacobs, J., . . . Klein, B. (2011). Vaccine-induced protection against 3 systemic mycoses endemic to North America requires Th17 cells in mice. The Journal of Clinical Investigation, 121(2), 554-568. doi:10.1172/JCI43984
Department
Molecular Microbiology and Immunology