Interleukin-22 mediates early host defense against Rhizomucor pusilluscan pathogens
In recent years, the fungal infectious disease zygomycosis has increased in incidence worldwide, especially among the immunodeficient population. Despite the rates of zygomycosis-related death and deformation being very high, the mechanism(s) by which the fungal pathogens cause these severe manifest...
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Published in | PloS one Vol. 8; no. 6; p. e65065 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Public Library of Science
17.06.2013
Public Library of Science (PLoS) |
Subjects | |
Online Access | Get full text |
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Summary: | In recent years, the fungal infectious disease zygomycosis has increased in incidence worldwide, especially among the immunodeficient population. Despite the rates of zygomycosis-related death and deformation being very high, the mechanism(s) by which the fungal pathogens cause these severe manifestations remain unknown.
Using the associated Rhizomucor variabilis species, which can selectively induce cutaneous zygomycosis in otherwise healthy individuals, we investigated the host mechanisms of infection-related responses, including cytokine and chemokine expression as well as contributions of particular T cell subsets. siRNA specifically targeting IL-22,IL-17 and IFN-γ were used to down-regulate expression of those molecules.
In mouse models of infection, IL-22 was implicated in development of Rhizomucor spp.-induced skin lesions. In cultured human peripheral blood monocytes, R. pusilluscan, which is often found in immunodeficient patients, induced the production of IL-22, while R. variabilis did not. Moreover, Rhizomucor spp.-induced secretion of Il-22 from CCR6(+)CCR4(+)CCR10(+) cells was down-regulated by knockdown of IL-22 related signaling receptors, RORC and ARH.
Our data strongly suggest that avoidance of IL-22 may be one mechanism by which mucor species produce morbidity and mortality in infected individuals. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Conceived and designed the experiments: WL WB. Performed the experiments: WB LJ HF. Analyzed the data: WB LJ HF WL. Contributed reagents/materials/analysis tools: XC HM YS GL HW. Wrote the paper: WB WL. Competing Interests: The authors have declared that no competing interests exist. |
ISSN: | 1932-6203 1932-6203 |
DOI: | 10.1371/journal.pone.0065065 |