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- W4313366389 abstract "Abstract Cryptococcus neoformans is an opportunistic fungal pathogen that causes cryptococcal pneumonia in immunocompromised and immunocompetent individuals. We previously have shown that mice given an experimental pulmonary infection with a genetically modified strain of H99 that produces murine IFN-γ, H99γ, are able to completely resolve the pulmonary infection via the upregulation of the IFN-γ/STAT1 signaling pathway. Activation of STAT1 signaling leads to the production of CXCL9, CXCL10 and CXCL11 chemokines. These chemokines each serve as ligands for the CXCR3 receptor that is present on host immune cells including T cells, NK cells, dendritic cells (DCs) and plasmacytoid DCs and facilitate their chemotaxis to the site of infection. C57BL/6 (B6) mice produce a non-functional CXCL11 protein. Our studies show that B6 mice infected with C. neoformans strain H99γ have a 40% survival, compared to 100% survival in BALB/c mice and an 80% survival of F1 generation mice (first generation of BALB/c × B6) at day 60-post inoculation. After 60 days post-inoculation F1 mice infected with H99γ had a significant decrease in fungal burden compared to B6 mice. We also demonstrated that B6 mice do not produce CXCL11, as expected, at day 7 and 14 post-inoculation whereas F1 mice show a significant increase in the production of CXCL11 compared to B6 mice. Lastly, treatment of B6 mice given a pulmonary C. neoformans infection with recombinant CXCL11 resulted in a significant decrease in pulmonary fungal burden compared to untreated B6 mice infected with C. neoformans. These data suggest that activation of the STAT1-mediated signaling pathway and CXCL11 chemokine production is necessary for optimal protection against pulmonary C. neoformans infection." @default.
- W4313366389 created "2023-01-06" @default.
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- W4313366389 date "2018-05-01" @default.
- W4313366389 modified "2023-09-28" @default.
- W4313366389 title "Requirement of CXCL11 chemokine production for induction of protection against pulmonary cryptococcosis" @default.
- W4313366389 doi "https://doi.org/10.4049/jimmunol.200.supp.52.31" @default.
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