Dear Spiral user, We’re pleased to introduce Helix, https://helix.imperial.ac.uk/ Imperial’s new repository for research datasets. Please use Helix for all future dataset deposits. There is no change to Spiral - continue depositing as usual. For queries, contact the Research Data Management team at rdm-enquiries@imperial.ac.uk. Kind regards, the Spiral Team. The Spiral team
ESX1-dependent fractalkine mediates chemotaxis and Mycobacterium tuberculosis infection in humans
File(s)
Author(s)
Hingley-Wilson, Suzanne M
Connell, David
Pollock, Katrina
Hsu, Tsungda
Tchilian, Elma
Type
Journal Article
Abstract
Mycobacterium tuberculosis-induced cellular aggregation is essential for granuloma formation and may assist establishment and early spread of M. tuberculosis infection. The M. tuberculosis ESX1 mutant, which has a non-functional type VII secretion system, induced significantly less production of the host macrophage-derived chemokine fractalkine (CX3CL1). Upon infection of human macrophages ESX1-dependent fractalkine production mediated selective recruitment of CD11b+ monocytic cells and increased infection of neighbouring cells consistent with early local spread of infection. Fractalkine levels were raised in vivo at tuberculous disease sites in humans and were significantly associated with increased CD11b+ monocytic cellular recruitment and extent of granulomatous disease. These findings suggest a novel fractalkine-dependent ESX1-mediated mechanism in early tuberculous disease pathogenesis in humans. Modulation of M. tuberculosis-mediated fractalkine induction may represent a potential treatment option in the future, perhaps allowing us to switch off a key mechanism required by the pathogen to spread between cells.
Date Issued
2014-05-01
Date Acceptance
2014-01-27
Citation
TUBERCULOSIS, 2014, 94 (3), pp.262-270
URI
DOI
ISSN
1472-9792
Publisher
Elsevier
Start Page
262
End Page
270
Journal / Book Title
TUBERCULOSIS
Volume
94
Issue
3
Copyright Statement
© 2014 The Authors. Published by Elsevier Ltd.
Open access under CC BY license (https://creativecommons.org/licenses/by/3.0/).
Sponsor
Medical Research Council (MRC)
Medical Research Council (MRC)
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000335913700009&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
G0700552
G1001945
Subjects
Science & Technology
Life Sciences & Biomedicine
Immunology
Microbiology
Respiratory System
Tuberculosis
Fractalkine
Infection
Mycobacterium
ESX-1
GRANULOMA-FORMATION
CALMETTE-GUERIN
CHEMOKINE
MACROPHAGES
SURVIVAL
EXPRESSION
CX3CL1
ESAT-6/CFP-10
INDUCTION
VIRULENCE
Publication Status
Published
Date Publish Online
2014-02-03