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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
Microglia are not protective against cryptococcal meningitis
Nature Communications, Volume 14, No. 1, Article 7202, Year 2023
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Description
Microglia provide protection against a range of brain infections including bacteria, viruses and parasites, but how these glial cells respond to fungal brain infections is poorly understood. We investigated the role of microglia in the context of cryptococcal meningitis, the most common cause of fungal meningitis in humans. Using a series of transgenic- and chemical-based microglia depletion methods we found that, contrary to their protective role during other infections, loss of microglia did not affect control of Cryptococcus neoformans brain infection which was replicated with several fungal strains. At early time points post-infection, we found that microglia depletion lowered fungal brain burdens, which was related to intracellular residence of C. neoformans within microglia. Further examination of extracellular and intracellular fungal populations revealed that C. neoformans residing in microglia were protected from copper starvation, whereas extracellular yeast upregulated copper transporter CTR4. However, the degree of copper starvation did not equate to fungal survival or abundance of metals within different intracellular niches. Taken together, these data show how tissue-resident myeloid cells may influence fungal phenotype in the brain but do not provide protection against this infection, and instead may act as an early infection reservoir. © 2023, The Author(s).
Authors & Co-Authors
Bojang, Ebrima
United Kingdom, Birmingham
University of Birmingham
Lukande, Robert L.
Uganda, Kampala
Makerere University
Ballou, Elizabeth Ripley
United Kingdom, Exeter
University of Exeter
May, Robin Charles
United Kingdom, Birmingham
University of Birmingham
Vande Velde, Greetje
Belgium, Leuven
Molecular Small Animal Imaging Center
Drummond, Rebecca A.
United Kingdom, Birmingham
University of Birmingham
Statistics
Authors: 6
Affiliations: 5
Identifiers
Doi:
10.1038/s41467-023-43061-0
ISSN:
20411723