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Tuberculosis (Edinb). 2014 May;94(3):262-70. doi: 10.1016/j.tube.2014.01.004. Epub 2014 Feb 3.

ESX1-dependent fractalkine mediates chemotaxis and Mycobacterium tuberculosis infection in humans.

Author information

  • 1Tuberculosis Research Centre, Department of Respiratory Medicine, National Heart and Lung Institute, Imperial College London, London W2 1PG, United Kingdom. Electronic address: s.hingley-wilson@surrey.ac.uk.
  • 2Tuberculosis Research Centre, Department of Respiratory Medicine, National Heart and Lung Institute, Imperial College London, London W2 1PG, United Kingdom.
  • 3Howard Hughes Medical Institute, Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY 10461, USA.
  • 4University of Oxford, Nuffield Department of Medicine, The Peter Medawar Building for Pathogen Research, South Parks Road, Oxford OX1 3SY, United Kingdom.
  • 5Tuberculosis Service, St Mary's Hospital, Imperial College Healthcare, National Health Service Trust, London W2 1PG, United Kingdom.

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.

Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

KEYWORDS:

ESX-1; Fractalkine; Infection; Mycobacterium; Tuberculosis

PMID:
24631198
[PubMed - indexed for MEDLINE]
PMCID:
PMC4066952
Free PMC Article
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