Product Reference
IL-23 Dampens the Allergic Response to Cryptococcus neoformans through IL-17-Independent and -Dependent Mechanisms.
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| Author |
Szymczak, Wendy A, et al. |
| Citation Information |
Am. J. Pathol., 180: 1547-59 (2012), : (2012) |
| Related Products |
PHCC20040, PHCC20060 |
| Pub Med ID |
22342846 |
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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.
