Paradoxical Immune Responses in Non-HIV Cryptococcal Meningitis

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Cryptococcus is an important cause of fungal meningitis with significant mortality globally. Susceptibility to the fungus in humans has been related to T-lymphocyte defects in HIV-infected individuals, but little is known about possible immune defects in non HIV-infected patients including previously healthy individuals. This latter group also has some of the worst response rates to therapy with almost a third dying in the United States, despite available therapy. Here we conducted the first detailed immunological analysis of non-HIV apparently immunocompetent individuals with active cryptococcal disease. In contrast to HIV-infected individuals, these studies identified a highly activated antigen-presenting dendritic cell population within CSF, accompanied by a highly active T-lymphocyte population with potentially damaging inflammatory cytokine responses. Furthermore, elevated levels of CSF neurofilament light chains (NFL), a marker of axonal damage in severe central nervous system infections suggest a dysfunctional role to this acute inflammatory state. Paradoxically, CSF macrophage proportions were reduced in patients with severe disease and biopsy and autopsy samples identified alternatively activated tissue macrophage populations that failed to appropriately phagocytose fungal cells. Our study thus provides new insights into the susceptibility to human cryptococcal disease and identifies a paradoxically active T-lymphocyte response that may be amenable to adjunctive immunomodulation to improve treatment outcomes in this high-mortality disease.

Vyšlo v časopise: Paradoxical Immune Responses in Non-HIV Cryptococcal Meningitis. PLoS Pathog 11(5): e32767. doi:10.1371/journal.ppat.1004884
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004884

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