Journal of Extracellular Vesicles (Jan 2021)
Dissemination of Mycobacterium tuberculosis is associated to a SIGLEC1 null variant that limits antigen exchange via trafficking extracellular vesicles
- Susana Benet,
- Cristina Gálvez,
- Francis Drobniewski,
- Irina Kontsevaya,
- Lilibeth Arias,
- Marta Monguió‐Tortajada,
- Itziar Erkizia,
- Victor Urrea,
- Ruo‐Yan Ong,
- Marina Luquin,
- Maeva Dupont,
- Jakub Chojnacki,
- Judith Dalmau,
- Paula Cardona,
- Olivier Neyrolles,
- Geanncarlo Lugo‐Villarino,
- Christel Vérollet,
- Esther Julián,
- Hansjakob Furrer,
- Huldrych F. Günthard,
- Paul R. Crocker,
- Gustavo Tapia,
- Francesc E. Borràs,
- Jacques Fellay,
- Paul J. McLaren,
- Amalio Telenti,
- Pere‐Joan Cardona,
- Bonaventura Clotet,
- Cristina Vilaplana,
- Javier Martinez‐Picado,
- Nuria Izquierdo‐Useros
Affiliations
- Susana Benet
- Department of Retrovirology IrsiCaixa AIDS Research Institute Badalona Spain
- Cristina Gálvez
- Department of Retrovirology IrsiCaixa AIDS Research Institute Badalona Spain
- Francis Drobniewski
- Department of Retrovirology Imperial College London UK
- Irina Kontsevaya
- Department of Retrovirology Imperial College London UK
- Lilibeth Arias
- Experimental Tuberculosis Unit (UTE) Germans Trias i Pujol Health Science Research Institute Can Ruti Campus Badalona Spain
- Marta Monguió‐Tortajada
- REMAR‐IVECAT Group Germans Trias i Pujol Health Science Research Institute Can Ruti Campus Badalona Spain
- Itziar Erkizia
- Department of Retrovirology IrsiCaixa AIDS Research Institute Badalona Spain
- Victor Urrea
- Department of Retrovirology IrsiCaixa AIDS Research Institute Badalona Spain
- Ruo‐Yan Ong
- Division of Cell Signalling and Immunology University of Dundee Dundee UK
- Marina Luquin
- Departament de Genètica i de Microbiologia Facultat de Biociències Universitat Autònoma de Barcelona Cerdanyola del Vallès Spain
- Maeva Dupont
- Institut de Pharmacologie et Biologie Structurale IPBS CNRS UPS Université de Toulouse Toulouse France
- Jakub Chojnacki
- Department of Retrovirology IrsiCaixa AIDS Research Institute Badalona Spain
- Judith Dalmau
- Department of Retrovirology IrsiCaixa AIDS Research Institute Badalona Spain
- Paula Cardona
- Experimental Tuberculosis Unit (UTE) Germans Trias i Pujol Health Science Research Institute Can Ruti Campus Badalona Spain
- Olivier Neyrolles
- Institut de Pharmacologie et Biologie Structurale IPBS CNRS UPS Université de Toulouse Toulouse France
- Geanncarlo Lugo‐Villarino
- Institut de Pharmacologie et Biologie Structurale IPBS CNRS UPS Université de Toulouse Toulouse France
- Christel Vérollet
- Institut de Pharmacologie et Biologie Structurale IPBS CNRS UPS Université de Toulouse Toulouse France
- Esther Julián
- Departament de Genètica i de Microbiologia Facultat de Biociències Universitat Autònoma de Barcelona Cerdanyola del Vallès Spain
- Hansjakob Furrer
- Department of Infectious Diseases Bern University Hospital University of Bern Bern Switzerland
- Huldrych F. Günthard
- Division of Infectious Diseases and Hospital Epidemiology University Hospital Zurich Zurich Switzerland
- Paul R. Crocker
- Division of Cell Signalling and Immunology University of Dundee Dundee UK
- Gustavo Tapia
- Department of Retrovirology Universitat Autònoma de Barcelona Cerdanyola del Vallès Spain
- Francesc E. Borràs
- REMAR‐IVECAT Group Germans Trias i Pujol Health Science Research Institute Can Ruti Campus Badalona Spain
- Jacques Fellay
- School of Life Sciences École Polytechnique Fédérale de Lausanne Lausanne Switzerland
- Paul J. McLaren
- JC Wilt Infectious Diseases Research Centre Public Health Agency of Canada Winnipeg Manitoba Canada
- Amalio Telenti
- The Scripps Research Institute La Jolla California USA
- Pere‐Joan Cardona
- Experimental Tuberculosis Unit (UTE) Germans Trias i Pujol Health Science Research Institute Can Ruti Campus Badalona Spain
- Bonaventura Clotet
- Department of Retrovirology IrsiCaixa AIDS Research Institute Badalona Spain
- Cristina Vilaplana
- Experimental Tuberculosis Unit (UTE) Germans Trias i Pujol Health Science Research Institute Can Ruti Campus Badalona Spain
- Javier Martinez‐Picado
- Department of Retrovirology IrsiCaixa AIDS Research Institute Badalona Spain
- Nuria Izquierdo‐Useros
- Department of Retrovirology IrsiCaixa AIDS Research Institute Badalona Spain
- DOI
- https://doi.org/10.1002/jev2.12046
- Journal volume & issue
-
Vol. 10,
no. 3
pp. n/a – n/a
Abstract
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
