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Dissemination of Mycobacterium tuberculosis is associated to a SIGLEC1 null variant that limits antigen exchange via trafficking extracellular vesicles
Author(s) -
Benet Susana,
Gálvez Cristina,
Drobniewski Francis,
Kontsevaya Irina,
Arias Lilibeth,
MonguióTortajada Marta,
Erkizia Itziar,
Urrea Victor,
Ong RuoYan,
Luquin Marina,
Dupont Maeva,
Chojnacki Jakub,
Dalmau Judith,
Cardona Paula,
Neyrolles Olivier,
LugoVillarino Geanncarlo,
Vérollet Christel,
Julián Esther,
Furrer Hansjakob,
Günthard Huldrych F.,
Crocker Paul R.,
Tapia Gustavo,
Borràs Francesc E.,
Fellay Jacques,
McLaren Paul J.,
Telenti Amalio,
Cardona PereJoan,
Clotet Bonaventura,
Vilaplana Cristina,
MartinezPicado Javier,
IzquierdoUseros Nuria
Publication year - 2021
Publication title -
journal of extracellular vesicles
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.94
H-Index - 68
ISSN - 2001-3078
DOI - 10.1002/jev2.12046
Subject(s) - mycobacterium tuberculosis , biology , null allele , extracellular , null cell , antigen , immunology , tuberculosis , microbiology and biotechnology , mutant , gene , genetics , medicine , pathology
The identification of individuals with null alleles enables studying how the loss of gene function affects infection. We previously described a non‐functional variant in SIGLEC1 , which encodes the myeloid‐cell receptor Siglec‐1/CD169 implicated in HIV‐1 cell‐to‐cell transmission. Here we report a significant association between the SIGLEC1 null variant and extrapulmonary dissemination of Mycobacterium tuberculosis (Mtb) in two clinical cohorts comprising 6,256 individuals. Local spread of bacteria within the lung is apparent in Mtb‐infected Siglec‐1 knockout mice which, despite having similar bacterial load, developed more extensive lesions compared to wild type mice. We find that Siglec‐1 is necessary to induce antigen presentation through extracellular vesicle uptake. We postulate that lack of Siglec‐1 delays the onset of protective immunity against Mtb by limiting antigen exchange via extracellular vesicles, allowing for an early local spread of mycobacteria that increases the risk for extrapulmonary dissemination.

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