title: IL-23 dampens the allergic response to Cryptococcus neoformans through IL-17-independent and -dependent mechanisms.
abstract: The cytokines IL-23 and IL-17 have been implicated in resistance to cryptococcal disease, but it is not clear whether IL-23-mediated production of IL-17 promotes fungal containment following pulmonary challenge with Cryptococcus neoformans. We used mice lacking IL-23 (IL-23p19(-/-)) or IL-17RA (IL-17RA(-/-)), and wild type (WT) C57BL/6 mice to examine the IL-23/IL-17 axis after intranasal infection with the C. neoformans strain 52D. The absence of IL-23 or IL-17RA had no effect on pulmonary or brain fungal burden at 1 or 6 weeks after infection. However, survival of IL-23p19(-/-) mice was reduced compared to IL-17RA(-/-) mice. IL-I7 production by CD4 T cells and natural killer T (NKT) cells was impaired in IL-23p19(-/-) lungs, but was not completely abolished. Both IL-23p19(-/-) and IL-17RA(-/-) mice exhibited impaired neutrophil recruitment, increased serum levels of IgE and IgG2b, and increased deposition of YM1/YM2 crystals in the lung, but only IL-23p19(-/-) mice developed persistent lung eosinophilia. Although survival of IL-17RA(-/-) and WT mice was similar after 17 weeks of infection, only surviving IL-17RA(-/-) mice exhibited cryptococcal dissemination to the blood. These data demonstrate that IL-23 dampens the allergic response to cryptococcal infection through IL-17-independent suppression of eosinophil recruitment and IL-17-dependent regulation of antibody production and crystal deposition. Furthermore, IL-23, and to a lesser extent IL-17, contribute to disease resistance.
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA. l.pirofski@einstein.yu.edu
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Szymczak
authors.forename: Rani S
authors.initials: RS
authors.lastname: Sellers
authors.forename: Liise-anne
authors.initials: LA
authors.lastname: Pirofski
mesh_terms: D000818:Animals; D000908:Antibodies, Fungal / Q000096:biosynthesis; D001921:Brain / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003453:Cryptococcosis / Q000276:immunology* / Q000473:pathology; D003455:Cryptococcus neoformans / Q000276:immunology* / Q000302:isolation & purification; D003460:Crystallization; D004195:Disease Models, Animal; D007073:Immunoglobulin E / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology*; D053759:Interleukin-23 / Q000172:deficiency / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D007962:Leukocytes / Q000276:immunology; D008168:Lung / Q000276:immunology; D008172:Lung Diseases, Fungal / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011657:Pulmonary Eosinophilia / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D053722:Receptors, Interleukin-17 / Q000172:deficiency / Q000276:immunology
chemical_list: D000908:Antibodies, Fungal; D020381:Interleukin-17; D053759:Interleukin-23; D053722:Receptors, Interleukin-17; D007073:Immunoglobulin E