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Comparative miRNA transcriptomics of macaques and mice reveals is an inhibitor for invasion into the brain. | LitMetric

AI Article Synopsis

  • Cryptococcal meningoencephalitis (CM) is increasingly affecting HIV/AIDS patients and others with weakened immune systems, but the processes behind its severity in the brain are not fully understood.
  • Researchers used macaque and mouse models to study immune responses to the infection, focusing on how the cytoskeleton is linked to disease progression in these patients.
  • The study found that certain immune cells work as a “Trojan Horse” to enhance fungal spread in the brain, and identified potential therapeutic targets, including the cytoskeleton and specific genetic factors, to combat this severe infection.

Article Abstract

Cryptococcal meningoencephalitis (CM) is emerging as an infection in HIV/AIDS patients shifted from primarily ART-naive to ART-experienced individuals, as well as patients with COVID-19 and immunocompetent hosts. This fungal infection is mainly caused by the opportunistic human pathogen . Brain or central nervous system (CNS) dissemination is the deadliest process for this disease; however, mechanisms underlying this process have yet to be elucidated. Moreover, illustrations of clinically relevant responses in cryptococcosis are currently limited due to the low availability of clinical samples. In this study, to explore the clinically relevant responses during infection, macaque and mouse infection models were employed and miRNA-mRNA transcriptomes were performed and combined, which revealed cytoskeleton, a major feature of HIV/AIDS patients, was a centric pathway regulated in both infection models. Notably, assays of clinical immune cells confirmed an enhanced macrophage "Trojan Horse" in patients with HIV/AIDS, which could be shut down by cytoskeleton inhibitors. Furthermore, myocilin, encoded by , was found to be a novel enhancer for the macrophage "Trojan Horse," and an enhanced fungal burden was achieved in the brains of -transgenic mice. Taken together, the findings from this study reveal fundamental roles of the cytoskeleton and in fungal CNS dissemination, which not only helps to understand the high prevalence of CM in HIV/AIDS but also facilitates the development of novel therapeutics for meningoencephalitis caused by and other pathogenic microorganisms.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9176638PMC
http://dx.doi.org/10.1080/22221751.2022.2081619DOI Listing

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