Dissemination of Mycobacterium tuberculosis is associated to a SIGLEC1 null variant that limits antigen exchange via trafficking extracellular vesicles.

Details

Ressource 1Download: Fellay_jev2.12046.pdf (2791.76 [Ko])
State: Public
Version: Final published version
License: CC BY-NC 4.0
Serval ID
serval:BIB_3994DD1EFC01
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Dissemination of Mycobacterium tuberculosis is associated to a SIGLEC1 null variant that limits antigen exchange via trafficking extracellular vesicles.
Journal
Journal of extracellular vesicles
Author(s)
Benet S., Gálvez C., Drobniewski F., Kontsevaya I., Arias L., Monguió-Tortajada M., Erkizia I., Urrea V., Ong R.Y., Luquin M., Dupont M., Chojnacki J., Dalmau J., Cardona P., Neyrolles O., Lugo-Villarino G., Vérollet C., Julián E., Furrer H., Günthard H.F., Crocker P.R., Tapia G., Borràs F.E., Fellay J., McLaren P.J., Telenti A., Cardona P.J., Clotet B., Vilaplana C., Martinez-Picado J., Izquierdo-Useros N.
ISSN
2001-3078 (Print)
ISSN-L
2001-3078
Publication state
Published
Issued date
01/2021
Peer-reviewed
Oui
Volume
10
Number
3
Pages
e12046
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
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.
Keywords
Extracellular vesicles, HIV‐1, Mtb, Siglec‐1
Pubmed
Web of science
Open Access
Yes
Create date
19/02/2021 10:55
Last modification date
26/02/2021 7:08
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