Interleukin-22 mediates early host defense against Rhizomucor pusilluscan pathogens

• Published in: PloS one 2013-06, Vol.8 (6), p.e65065-e65065
• Main Authors: Bao, Wei, Jin, Lei, Fu, Hai-jing, Shen, Yong-nian, Lu, Gui-xia, Mei, Huan, Cao, Xin-zhi, Wang, Hong-sheng, Liu, Wei-da
• Format: Article
• Language: English
• Subjects: Analysis; Animal models; Animals; Antifungal agents; Bacterial infections; Base Sequence; Biology; Candida albicans; CCR6 protein; CD4-Positive T-Lymphocytes - immunology; Communicable diseases; Cytokines; Cytokines - biosynthesis; Deformation; Deformation mechanisms; Dermatology; Disease Models, Animal; DNA Primers; Flow Cytometry; Fungi; Gene expression; Health aspects; Hospitals; Hydrocarbons; Immunodeficiency; Infection; Infections; Infectious diseases; Interferon; Interleukin 17; Interleukin 22; Interleukins; Interleukins - biosynthesis; Interleukins - genetics; Interleukins - physiology; Laboratories; Lesions; Ligands; Lymphocytes; Lymphocytes T; Medical research; Medicine; Mice; Mice, Inbred BALB C; Molecular biology; Molecular modelling; Monocytes; Morbidity; Mucormycosis - immunology; Mucormycosis - microbiology; Pathogenic microorganisms; Pathogens; Peripheral blood; Receptors; Rhizomucor - immunology; RNA, Small Interfering - genetics; Rodents; Signaling; siRNA; Skin; Skin diseases; T cells; Viral infections; Zygomycosis; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0065065

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.