Requirement of interleukin-17A for systemic anti-Candida albicans host defense in mice.
T cells are required for normal host defense against fungal infection, and individuals with T cell-deficiency syndromes are highly susceptible to fungal pathogens. Interleukin (IL)-17A is a proinflammatory cytokine that interconnects myeloid and lymphoid host defense. The role of murine (m) IL-17A/mIL-17A receptor (R) interactions was evaluated in a murine model of systemic candidiasis. In response to systemic challenge with Candida albicans, expression of mIL-17A was induced, and IL-17AR knockout (IL-17AR(-/-)) mice had dose-dependent, substantially reduced survival. Fungal burden in the kidneys of IL-17AR(-/-) mice was dramatically increased (25-fold at 96 h). In IL-17AR(-/-) mice, both mobilization of peripheral neutrophils and their influx to infected organs were significantly impaired and delayed. In vivo expression of mIL-17A protected normal mice from a lethal dose of C. albicans (100% at day 7 and 65% at day 42). The data suggest that the mIL-17A/mIL-17AR system is required for normal fungal host defense in vivo. IL-17A could have potential as a therapeutic cytokine for systemic C. albicans infections in immunocompromised patients with cancer or advanced acquired immunodeficiency syndrome.
Huang
Weitao
W
Gene Therapy Program, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70122, USA.
Na
Li
L
Fidel
Paul L
PL
Schwarzenberger
Paul
P
D000818:Animals; D002176:Candida albicans / Q000472:pathogenicity*; D002177:Candidiasis / Q000276:immunology* / Q000401:mortality; D004195:Disease Models, Animal; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D007668:Kidney / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism*; D053722:Receptors, Interleukin-17; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*
C109985:IL17RA protein, human; C491673:Il17ra protein, mouse; D020381:Interleukin-17; D018123:Receptors, Interleukin; D053722:Receptors, Interleukin-17; D011994:Recombinant Proteins