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

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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-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.

Original languageEnglish (US)
Pages (from-to)1547-1559
Number of pages13
JournalAmerican Journal of Pathology
Volume180
Issue number4
DOIs
StatePublished - Apr 2012

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Interleukin-23
Cryptococcus neoformans
Interleukin-23 Subunit p19
Interleukin-17
Lung
Infection
Natural Killer T-Cells
Disease Resistance
Neutrophil Infiltration
Eosinophilia
Inbred C57BL Mouse
Eosinophils
Immunoglobulin E
Antibody Formation
Cytokines
T-Lymphocytes
Brain
Serum

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

@article{6818f105e0ad485b918c3a72786fc754,
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-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.",
author = "Szymczak, {Wendy A.} and Sellers, {Rani S.} and Liise-anne Pirofski",
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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

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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