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

Suzanne M. Hingley-Wilson, David Connell, Katrina Pollock, Tsungda Hsu, Elma Tchilian, Anny Sykes, Lisa Grass, Lee Potiphar, Samuel Bremang, Onn Min Kon, William R. Jacobs, Ajit Lalvani

Research output: Contribution to journalArticle

4 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)262-270
Number of pages9
JournalTuberculosis
Volume94
Issue number3
DOIs
StatePublished - May 2014

Keywords

  • ESX-1
  • Fractalkine
  • Infection
  • Mycobacterium
  • Tuberculosis

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

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    Hingley-Wilson, S. M., Connell, D., Pollock, K., Hsu, T., Tchilian, E., Sykes, A., Grass, L., Potiphar, L., Bremang, S., Kon, O. M., Jacobs, W. R., & Lalvani, A. (2014). ESX1-dependent fractalkine mediates chemotaxis and Mycobacterium tuberculosis infection in humans. Tuberculosis, 94(3), 262-270. https://doi.org/10.1016/j.tube.2014.01.004