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

dc.contributor.authorWüthrich, Marcel
dc.contributor.authorGern, Benjamin
dc.contributor.authorHung, Chiung-Yu
dc.contributor.authorErsland, Karen
dc.contributor.authorRocco, Nicole
dc.contributor.authorPick-Jacobs, John
dc.contributor.authorGalles, Kevin
dc.contributor.authorFilutowicz, Hanna
dc.contributor.authorWarner, Thomas
dc.contributor.authorEvans, Michael
dc.contributor.authorCole, Garry T.
dc.contributor.authorKlein, Bruce
dc.creator.orcidhttps://orcid.org/0000-0003-1091-3420en_US
dc.date.accessioned2023-06-29T16:46:19Z
dc.date.available2023-06-29T16:46:19Z
dc.date.issued2011-01-04
dc.description.abstractWorldwide 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.en_US
dc.description.departmentMolecular Microbiology and Immunologyen_US
dc.identifier.citationWüthrich, 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/JCI43984en_US
dc.identifier.issn1558-8238
dc.identifier.otherhttps://doi.org/10.1172/jci43984
dc.identifier.urihttps://hdl.handle.net/20.500.12588/1964
dc.language.isoen_USen_US
dc.publisherAmerican Society for Clinical Investigationen_US
dc.relation.ispartofseriesThe Journal of Clinical Investigation;Volume 121, Issue 2
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.subjectCoccidioides posadasiien_US
dc.subjectHistoplasma capsulatumen_US
dc.subjectBlastomyces dermatitidisen_US
dc.titleVaccine-induced protection against 3 systemic mycoses endemic to North America requires Th17 cells in miceen_US
dc.typeArticleen_US

Files

Original bundle

Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
Wüthrich 2011 - Vaccine-induced protection against 3 systemic mycoses endemic to North America requires Th17 cells in mice.pdf
Size:
2.14 MB
Format:
Adobe Portable Document Format
Description:

License bundle

Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.86 KB
Format:
Item-specific license agreed upon to submission
Description: