Loss of the scavenger receptor MARCO results in uncontrolled vomocytosis of fungi from macrophages

Chinaemerem U Onyishi; Yusun Jeon; Gyorgy Fejer; Subhankar Mukhopadhyay; Siamon Gordon; Robin C May

doi:10.1002/eji.202350771

Loss of the scavenger receptor MARCO results in uncontrolled vomocytosis of fungi from macrophages

Eur J Immunol. 2024 Mar 17:e2350771. doi: 10.1002/eji.202350771. Online ahead of print.

Authors

Chinaemerem U Onyishi^{1

2}, Yusun Jeon³, Gyorgy Fejer⁴, Subhankar Mukhopadhyay³, Siamon Gordon^{5

6}, Robin C May¹

Affiliations

¹ Institute of Microbiology & Infection and School of Biosciences, University of Birmingham, Edgbaston, Birmingham, UK.
² Molecular Mycology and Immunity Section, Laboratory of Host Immunity and Microbiome, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD, USA.
³ Peter Gorer Department of Immunobiology, School of Immunology & Microbial Sciences, King's College London, London, UK.
⁴ School of Biomedical Sciences, Faculty of Health, University of Plymouth, Plymouth, UK.
⁵ Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
⁶ Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.

PMID: 38494423
DOI: 10.1002/eji.202350771

Abstract

Vomocytosis, also known as nonlytic exocytosis, is a process whereby fully phagocytosed microbes are expelled from phagocytes without discernible damage to either the phagocyte or microbe. Although this phenomenon was first described in the opportunistic fungal pathogen Cryptococcus neoformans in 2006, to date, mechanistic studies have been hampered by an inability to reliably stimulate or inhibit vomocytosis. Here we present the fortuitous discovery that macrophages lacking the scavenger receptor MAcrophage Receptor with COllagenous domain (MARCO), exhibit near-total vomocytosis of internalised cryptococci within a few hours of infection. Marco^-/- macrophages also showed elevated vomocytosis of a yeast-locked C. albicans strain, suggesting this to be a broadly relevant observation. We go on to show that MARCO's role in modulating vomocytosis is independent of its role as a phagocytic receptor, suggesting that this protein may play an important and hitherto unrecognised role in modulating macrophage behaviour.

Keywords: Cryptococcus; Fungal pathogen; Innate immunity; MARCO; Macrophage; Vomocytosis.

Abstract

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