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Microglia are not protective against cryptococcal meningitis

Author

Listed:
  • Sally H. Mohamed

    (University of Birmingham)

  • Man Shun Fu

    (University of Birmingham)

  • Sofia Hain

    (University of Birmingham)

  • Alanoud Alselami

    (University of Birmingham)

  • Eliane Vanhoffelen

    (Biomedical MRI/MoSAIC, KU Leuven)

  • Yanjian Li

    (Northeastern University)

  • Ebrima Bojang

    (University of Birmingham)

  • Robert Lukande

    (Makerere University)

  • Elizabeth R. Ballou

    (University of Exeter)

  • Robin C. May

    (University of Birmingham)

  • Chen Ding

    (Northeastern University)

  • Greetje Vande Velde

    (Biomedical MRI/MoSAIC, KU Leuven)

  • Rebecca A. Drummond

    (University of Birmingham
    University of Birmingham)

Abstract

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.

Suggested Citation

  • Sally H. Mohamed & Man Shun Fu & Sofia Hain & Alanoud Alselami & Eliane Vanhoffelen & Yanjian Li & Ebrima Bojang & Robert Lukande & Elizabeth R. Ballou & Robin C. May & Chen Ding & Greetje Vande Velde, 2023. "Microglia are not protective against cryptococcal meningitis," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43061-0
    DOI: 10.1038/s41467-023-43061-0
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    References listed on IDEAS

    as
    1. Kanchan Bisht & Kenneth A. Okojie & Kaushik Sharma & Dennis H. Lentferink & Yu-Yo Sun & Hong-Ru Chen & Joseph O. Uweru & Saipranusha Amancherla & Zainab Calcuttawala & Antony Brayan Campos-Salazar & B, 2021. "Capillary-associated microglia regulate vascular structure and function through PANX1-P2RY12 coupling in mice," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
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    3. Samantha J. Batista & Katherine M. Still & David Johanson & Jeremy A. Thompson & Carleigh A. OʼBrien & John R. Lukens & Tajie H. Harris, 2020. "Gasdermin-D-dependent IL-1α release from microglia promotes protective immunity during chronic Toxoplasma gondii infection," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    4. Tian-Shu Sun & Xiao Ju & Hui-Ling Gao & Tao Wang & Dennis J. Thiele & Jia-Yi Li & Zhan-You Wang & Chen Ding, 2014. "Reciprocal functions of Cryptococcus neoformans copper homeostasis machinery during pulmonary infection and meningoencephalitis," Nature Communications, Nature, vol. 5(1), pages 1-13, December.
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