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Cryptococcal meningoencephalitis (CM) is the major cause of infection-related neurological death, typically seen in immunocompromised patients. However, T cell-driven inflammatory response has been increasingly implicated in lethal central nervous system (CNS) immunopathology in human patients and murine models. Here, we report marked up-regulation of the chemokine receptor CXCR3 axis in human patients and mice with CM. CXCR3 deletion in mice improves survival, diminishes neurological deficits, and limits neuronal damage without suppressing fungal clearance. CD4 T cell accumulation and T1 skewing are reduced in the CNS but not spleens of infected CXCR3 mice. Adoptive transfer of WT, but not CXCR3 CD4 T cells, into CXCR3 mice phenocopies the pathology of infected WT mice. Collectively, we found that CXCR3CD4 T cells drive lethal CNS pathology but are not required for fungal clearance during CM. The CXCR3 pathway shows potential as a therapeutic target or for biomarker discovery to limit CNS inflammatory damages.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299622 | PMC |
| http://dx.doi.org/10.1126/sciadv.aba2502 | DOI Listing |
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