Open AccessInterleukin-22 Mediates Early Host Defense against Rhizomucor pusilluscan Pathogens
Author(s) -
Wei Bao,
Lei Jin,
Haijing Fu,
Ya Shen,
Guixia Lu,
Huan Mei,
Xia Cao,
Hongsheng Wang,
Weida Liu
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0065065
Subject(s) - biology , chemokine , immunology , interleukin 22 , chemokine receptor , microbiology and biotechnology , zygomycosis , population , cytokine , interleukin , immune system , medicine , antifungal , amphotericin b , environmental health
Background 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. Methods 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. Results 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. Conclusion Our data strongly suggest that avoidance of IL-22 may be one mechanism by which mucor species produce morbidity and mortality in infected individuals.