The Rab32/BLOC-3–dependent pathway mediates host defense against different pathogens in human macrophages

Massimiliano Baldassarre* (Corresponding Author), Maria Virtudes Solano Collado, Arda Balci, Rosa Angela Colamarino, Ivy M. Dambuza, Delyth M Reid, Heather Wilson, Gordon D Brown, Subhankar Mukhopadyay, Gordon Dougan, Stefania Spano

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)
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Macrophages provide a first line of defense against microorganisms, and while some mechanisms to kill pathogens such as the oxidative burst are well described, others are still undefined or unknown. Here, we report that the Rab32 guanosine triphosphatase and its guanine nucleotide exchange factor BLOC-3 (biogenesis of lysosome-related organelles complex–3) are central components of a trafficking pathway that controls both bacterial and fungal intracellular pathogens. This host-defense mechanism is active in both human and murine macrophages and is independent of well-known antimicrobial mechanisms such as the NADPH (reduced form of nicotinamide adenine dinucleotide phosphate)–dependent oxidative burst, production of nitric oxide, and antimicrobial peptides. To survive in human macrophages, Salmonella Typhi actively counteracts the Rab32/BLOC-3 pathway through its Salmonella pathogenicity island-1–encoded type III secretion system. These findings demonstrate that the Rab32/BLOC-3 pathway is a novel and universal host-defense pathway and protects mammalian species from various pathogens.

Original languageEnglish
Article numbereabb1795
Number of pages9
JournalScience Advances
Issue number3
Publication statusPublished - 15 Jan 2021

Bibliographical note

Tenovus Scotland, GRANT #(s) G14/19; Royal Society, FUNDREF 10.13039/501100000288, GRANT #(s) RG150386;
Biotechnology and Biological Sciences Research Council, FUNDREF 10.13039/501100000268, GRANT #(s) BB/N017854/1;
Medical Research Council, FUNDREF 10.13039/501100000265, GRANT #(s) MR/N006364; H2020 European Research Council,
FUNDREF 10.13039/100010663, GRANT #(s) 706040_KILLINGTYPHI; H2020 European Research Council, FUNDREF
10.13039/100010663, GRANT #(s) 2016-726152-TYPHI; Wellcome, FUNDREF 10.13039/100010269, GRANT #(s) 102705;
Wellcome, FUNDREF 10.13039/100010269, GRANT #(s) 109680/Z/15/Z


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