RGD Reference Report - IL-23 dampens the allergic response to Cryptococcus neoformans through IL-17-independent and -dependent mechanisms. - Rat Genome Database

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IL-23 dampens the allergic response to Cryptococcus neoformans through IL-17-independent and -dependent mechanisms.

Authors: Szymczak, Wendy A  Sellers, Rani S  Pirofski, Liise-anne 
Citation: Szymczak WA, etal., Am J Pathol. 2012 Apr;180(4):1547-59. doi: 10.1016/j.ajpath.2011.12.038. Epub 2012 Feb 16.
RGD ID: 39458042
Pubmed: (View Article at PubMed) PMID:22342846
DOI: Full-text: DOI:10.1016/j.ajpath.2011.12.038

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.

Disease Annotations    
cryptococcosis  (IMP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Il23a  (interleukin 23 subunit alpha)

Genes (Mus musculus)
Il23a  (interleukin 23, alpha subunit p19)

Genes (Homo sapiens)
IL23A  (interleukin 23 subunit alpha)

Additional Information