RGD Reference Report - IL-23 enhances the inflammatory cell response in Cryptococcus neoformans infection and induces a cytokine pattern distinct from IL-12. - Rat Genome Database

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IL-23 enhances the inflammatory cell response in Cryptococcus neoformans infection and induces a cytokine pattern distinct from IL-12.

Authors: Kleinschek, Melanie A  Muller, Uwe  Brodie, Scott J  Stenzel, Werner  Kohler, Gabriele  Blumenschein, Wendy M  Straubinger, Reinhard K  McClanahan, Terrill  Kastelein, Robert A  Alber, Gottfried 
Citation: Kleinschek MA, etal., J Immunol. 2006 Jan 15;176(2):1098-106. doi: 10.4049/jimmunol.176.2.1098.
RGD ID: 39457936
Pubmed: (View Article at PubMed) PMID:16393998
DOI: Full-text: DOI:10.4049/jimmunol.176.2.1098

IL-23, a heterodimeric cytokine composed of the p40 subunit of IL-12 and a novel p19 subunit, has been shown to be a key player in models of autoimmune chronic inflammation. To investigate the role of IL-23 in host resistance during chronic fungal infection, wild-type, IL-12- (IL-12p35-/-), IL-23- (IL-23p19-/-), and IL-12/IL-23- (p40-deficient) deficient mice on a C57BL/6 background were infected with Cryptococcus neoformans. Following infection, p40-deficient mice demonstrated higher mortality than IL-12p35-/- mice. Reconstitution of p40-deficient mice with rIL-23 prolonged their survival to levels similar to IL-12p35-/- mice. IL-23p19-/- mice showed a moderately reduced survival time and delayed fungal clearance in the liver. Although IFN-gamma production was similar in wild-type and IL-23p19-/- mice, production of IL-17 was strongly impaired in the latter. IL-23p19-/- mice produced fewer hepatic granulomata relative to organ burden and showed defective recruitment of mononuclear cells to the brain. Moreover, activation of microglia cells and expression of IL-1beta, IL-6, and MCP-1 in the brain was impaired. These results show that IL-23 complements the more dominant role of IL-12 in protection against a chronic fungal infection by an enhanced inflammatory cell response and distinct cytokine regulation.



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