Dissemination of Mycobacterium tuberculosis is associated to a SIGLEC1 null variant that limits antigen exchange via trafficking extracellular vesicles
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 re...
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Format: | Article |
Language: | English |
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Taylor & Francis Group
2021-01-01
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Series: | Journal of Extracellular Vesicles |
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Online Access: | https://doi.org/10.1002/jev2.12046 |
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collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Dissemination of Mycobacterium tuberculosis is associated to a SIGLEC1 null variant that limits antigen exchange via trafficking extracellular vesicles Journal of Extracellular Vesicles Extracellular vesicles HIV‐1 Mtb Siglec‐1 |
author_facet |
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 |
author_sort |
Susana Benet |
title |
Dissemination of Mycobacterium tuberculosis is associated to a SIGLEC1 null variant that limits antigen exchange via trafficking extracellular vesicles |
title_short |
Dissemination of Mycobacterium tuberculosis is associated to a SIGLEC1 null variant that limits antigen exchange via trafficking extracellular vesicles |
title_full |
Dissemination of Mycobacterium tuberculosis is associated to a SIGLEC1 null variant that limits antigen exchange via trafficking extracellular vesicles |
title_fullStr |
Dissemination of Mycobacterium tuberculosis is associated to a SIGLEC1 null variant that limits antigen exchange via trafficking extracellular vesicles |
title_full_unstemmed |
Dissemination of Mycobacterium tuberculosis is associated to a SIGLEC1 null variant that limits antigen exchange via trafficking extracellular vesicles |
title_sort |
dissemination of mycobacterium tuberculosis is associated to a siglec1 null variant that limits antigen exchange via trafficking extracellular vesicles |
publisher |
Taylor & Francis Group |
series |
Journal of Extracellular Vesicles |
issn |
2001-3078 |
publishDate |
2021-01-01 |
description |
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. |
topic |
Extracellular vesicles HIV‐1 Mtb Siglec‐1 |
url |
https://doi.org/10.1002/jev2.12046 |
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doaj-e05bc9140fb041fdabbc667eb4e666c42021-04-20T13:45:16ZengTaylor & Francis GroupJournal of Extracellular Vesicles2001-30782021-01-01103n/an/a10.1002/jev2.12046Dissemination of Mycobacterium tuberculosis is associated to a SIGLEC1 null variant that limits antigen exchange via trafficking extracellular vesiclesSusana Benet0Cristina Gálvez1Francis Drobniewski2Irina Kontsevaya3Lilibeth Arias4Marta Monguió‐Tortajada5Itziar Erkizia6Victor Urrea7Ruo‐Yan Ong8Marina Luquin9Maeva Dupont10Jakub Chojnacki11Judith Dalmau12Paula Cardona13Olivier Neyrolles14Geanncarlo Lugo‐Villarino15Christel Vérollet16Esther Julián17Hansjakob Furrer18Huldrych F. Günthard19Paul R. Crocker20Gustavo Tapia21Francesc E. Borràs22Jacques Fellay23Paul J. McLaren24Amalio Telenti25Pere‐Joan Cardona26Bonaventura Clotet27Cristina Vilaplana28Javier Martinez‐Picado29Nuria Izquierdo‐Useros30Department of Retrovirology IrsiCaixa AIDS Research Institute Badalona SpainDepartment of Retrovirology IrsiCaixa AIDS Research Institute Badalona SpainDepartment of Retrovirology Imperial College London UKDepartment of Retrovirology Imperial College London UKExperimental Tuberculosis Unit (UTE) Germans Trias i Pujol Health Science Research Institute Can Ruti Campus Badalona SpainREMAR‐IVECAT Group Germans Trias i Pujol Health Science Research Institute Can Ruti Campus Badalona SpainDepartment of Retrovirology IrsiCaixa AIDS Research Institute Badalona SpainDepartment of Retrovirology IrsiCaixa AIDS Research Institute Badalona SpainDivision of Cell Signalling and Immunology University of Dundee Dundee UKDepartament de Genètica i de Microbiologia Facultat de Biociències Universitat Autònoma de Barcelona Cerdanyola del Vallès SpainInstitut de Pharmacologie et Biologie Structurale IPBS CNRS UPS Université de Toulouse Toulouse FranceDepartment of Retrovirology IrsiCaixa AIDS Research Institute Badalona SpainDepartment of Retrovirology IrsiCaixa AIDS Research Institute Badalona SpainExperimental Tuberculosis Unit (UTE) Germans Trias i Pujol Health Science Research Institute Can Ruti Campus Badalona SpainInstitut de Pharmacologie et Biologie Structurale IPBS CNRS UPS Université de Toulouse Toulouse FranceInstitut de Pharmacologie et Biologie Structurale IPBS CNRS UPS Université de Toulouse Toulouse FranceInstitut de Pharmacologie et Biologie Structurale IPBS CNRS UPS Université de Toulouse Toulouse FranceDepartament de Genètica i de Microbiologia Facultat de Biociències Universitat Autònoma de Barcelona Cerdanyola del Vallès SpainDepartment of Infectious Diseases Bern University Hospital University of Bern Bern SwitzerlandDivision of Infectious Diseases and Hospital Epidemiology University Hospital Zurich Zurich SwitzerlandDivision of Cell Signalling and Immunology University of Dundee Dundee UKDepartment of Retrovirology Universitat Autònoma de Barcelona Cerdanyola del Vallès SpainREMAR‐IVECAT Group Germans Trias i Pujol Health Science Research Institute Can Ruti Campus Badalona SpainSchool of Life Sciences École Polytechnique Fédérale de Lausanne Lausanne SwitzerlandJC Wilt Infectious Diseases Research Centre Public Health Agency of Canada Winnipeg Manitoba CanadaThe Scripps Research Institute La Jolla California USAExperimental Tuberculosis Unit (UTE) Germans Trias i Pujol Health Science Research Institute Can Ruti Campus Badalona SpainDepartment of Retrovirology IrsiCaixa AIDS Research Institute Badalona SpainExperimental Tuberculosis Unit (UTE) Germans Trias i Pujol Health Science Research Institute Can Ruti Campus Badalona SpainDepartment of Retrovirology IrsiCaixa AIDS Research Institute Badalona SpainDepartment of Retrovirology IrsiCaixa AIDS Research Institute Badalona SpainAbstract 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.https://doi.org/10.1002/jev2.12046Extracellular vesiclesHIV‐1MtbSiglec‐1 |