IL-22 defines a novel immune pathway of antifungal resistance.
The role of IL-17 and Th17 cells in immunity vs. pathology associated with the human commensal Candida albicans remains controversial. Both positive and negative effects on immune resistance have been attributed to IL-17/Th17 in experimental candidiasis. In this study, we provide evidence that IL-22, which is also produced by Th17 cells, has a critical, first-line defense in candidiasis by controlling the growth of infecting yeasts as well as by contributing to the host's epithelial integrity in the absence of acquired Th1-type immunity. The two pathways are reciprocally regulated, and IL-22 is upregulated under Th1 deficiency conditions and vice versa. Whereas both IL-17A and F are dispensable for antifungal resistance, IL-22 mediates protection in IL-17RA-deficient mice, in which IL-17A contributes to disease susceptibility. Thus, our findings suggest that protective immunity to candidiasis is made up of a staged response involving an early, IL-22-dominated response followed by Th1/Treg reactivity that will prevent fungal dissemination and supply memory.
De Luca
A
A
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
Zelante
T
T
D'Angelo
C
C
Zagarella
S
S
Fallarino
F
F
Spreca
A
A
Iannitti
R G
RG
Bonifazi
P
P
Renauld
J-C
JC
Bistoni
F
F
Puccetti
P
P
Romani
L
L
D000818:Animals; D002176:Candida albicans / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D002177:Candidiasis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D048708:Cell Growth Processes; D002478:Cells, Cultured; D006801:Humans; D018928:Immunity, Mucosal; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D053722:Receptors, Interleukin-17 / Q000235:genetics / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000382:microbiology; D018418:Th2 Cells / Q000276:immunology / Q000382:microbiology; D000097043:Interleukin-22
D020381:Interleukin-17; D007378:Interleukins; D053722:Receptors, Interleukin-17; D000097043:Interleukin-22; C491673:Il17ra protein, mouse