IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-43061-0.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-43061-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-43061-0?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    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.
    2. 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.
    3. Koichiro Haruwaka & Ako Ikegami & Yoshihisa Tachibana & Nobuhiko Ohno & Hiroyuki Konishi & Akari Hashimoto & Mami Matsumoto & Daisuke Kato & Riho Ono & Hiroshi Kiyama & Andrew J. Moorhouse & Junichi N, 2019. "Dual microglia effects on blood brain barrier permeability induced by systemic inflammation," Nature Communications, Nature, vol. 10(1), pages 1-17, 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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Fan Li & Jazlyn Gallego & Natasha N. Tirko & Jenna Greaser & Derek Bashe & Rudra Patel & Eric Shaker & Grace E. Valkenburg & Alanoud S. Alsubhi & Steven Wellman & Vanshika Singh & Camila Garcia Padill, 2024. "Low-intensity pulsed ultrasound stimulation (LIPUS) modulates microglial activation following intracortical microelectrode implantation," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    2. George Sideris-Lampretsas & Silvia Oggero & Lynda Zeboudj & Rita Silva & Archana Bajpai & Gopuraja Dharmalingam & David A. Collier & Marzia Malcangio, 2023. "Galectin-3 activates spinal microglia to induce inflammatory nociception in wild type but not in mice modelling Alzheimer’s disease," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    3. Janos Groh & Tassnim Abdelwahab & Yogita Kattimani & Michaela Hörner & Silke Loserth & Viktoria Gudi & Robert Adalbert & Fabian Imdahl & Antoine-Emmanuel Saliba & Michael Coleman & Martin Stangel & Mi, 2023. "Microglia-mediated demyelination protects against CD8+ T cell-driven axon degeneration in mice carrying PLP defects," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    4. Shannon Tansley & Sonali Uttam & Alba Ureña Guzmán & Moein Yaqubi & Alain Pacis & Marc Parisien & Haley Deamond & Calvin Wong & Oded Rabau & Nicole Brown & Lisbet Haglund & Jean Ouellet & Carlo Santag, 2022. "Single-cell RNA sequencing reveals time- and sex-specific responses of mouse spinal cord microglia to peripheral nerve injury and links ApoE to chronic pain," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    5. William A. Mills & AnnaLin M. Woo & Shan Jiang & Joelle Martin & Dayana Surendran & Matthew Bergstresser & Ian F. Kimbrough & Ukpong B. Eyo & Michael V. Sofroniew & Harald Sontheimer, 2022. "Astrocyte plasticity in mice ensures continued endfoot coverage of cerebral blood vessels following injury and declines with age," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    6. Qian Shen & Matthew J Beucler & Stephanie C Ray & Chad A Rappleye, 2018. "Macrophage activation by IFN-γ triggers restriction of phagosomal copper from intracellular pathogens," PLOS Pathogens, Public Library of Science, vol. 14(11), pages 1-26, November.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43061-0. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.