TY - JOUR
T1 - IL-23 dampens the allergic response to Cryptococcus neoformans through IL-17-independent and - Dependent mechanisms
AU - Szymczak, Wendy A.
AU - Sellers, Rani S.
AU - Pirofski, Liise Anne
N1 - Funding Information:
We thank the AECOM Flow Cytometry Core Facility under the support of the AECOM National Cancer Institute ( P30CA013330 ) for assistance with data acquisition.
PY - 2012/4
Y1 - 2012/4
N2 - The cytokines IL-23 and IL-17 have been implicated in resistance to cryptococcal disease, but it is not clear whether IL-23mediated 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-17dependent regulation of antibody production and crystal deposition. Furthermore, IL-23, and to a lesser extent IL-17, contribute to disease resistance.
AB - The cytokines IL-23 and IL-17 have been implicated in resistance to cryptococcal disease, but it is not clear whether IL-23mediated 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-17dependent regulation of antibody production and crystal deposition. Furthermore, IL-23, and to a lesser extent IL-17, contribute to disease resistance.
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U2 - 10.1016/j.ajpath.2011.12.038
DO - 10.1016/j.ajpath.2011.12.038
M3 - Article
C2 - 22342846
AN - SCOPUS:84859064942
SN - 0002-9440
VL - 180
SP - 1547
EP - 1559
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 4
ER -