Interleukins 17 and 23 influence the host response to Histoplasma capsulatum.
Host defenses against Histoplasma capsulatum require the action of several cytokines. Here, we explored the influence of interleukin (IL)-17 and IL-23 on immunity to H. capsulatum infection in mice. In lungs, synthesis of IL-17 was up-regulated during acute infection, and the cells producing it were predominantly CD3(+). Neutralization of IL-17A blunted fungal clearance but did not promote progressive infection. Decreased inflammatory cell recruitment and increased levels of IL-6 and IL-10 were associated with impaired clearance. To determine whether the elevated cytokine levels were important in the action of IL-17A, IL-6(-/-) or IL-10(-/-) mice were treated with anti-IL-17A; neutralization of IL-17A did not alter fungal burden in either group of knockout mice. We explored the relationship between IL-17 and IL-23 because they have been reported to form a regulatory network. IL-23 transcription and protein level were increased in the lungs of infected mice. Mice producing IL-23 in the absence of IL-12 manifested prolonged survival that was IL-17 dependent. Thus, IL-17 is requisite for the generation of optimal inflammatory and protective responses. Generation of functional IL-17(+) cells is dependent on IL-6 and IL-10. Our findings also establish the existence a regulatory IL-17/IL-23 axis in histoplasmosis.
Deepe
George S
GS
Division of Infectious Diseases, Veterans Affairs Hospital, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0560, USA. george.deepe@uc.edu
Gibbons
Reta S
RS
D000818:Animals; D016207:Cytokines / Q000276:immunology; D006658:Histoplasma; D006660:Histoplasmosis / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology*; D053759:Interleukin-23 / Q000276:immunology*; D007378:Interleukins / Q000172:deficiency / Q000276:immunology; D008171:Lung Diseases / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051381:Rats
D016207:Cytokines; D020381:Interleukin-17; D053759:Interleukin-23; D007378:Interleukins