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

Hingley-Wilson, SM, Connell, D, Pollock, K, Grass, L, Potiphar, L, Bremang, S, Lalvani, A, Hsu, T, Jacobs Jr, WR, Tchilian, E , Sykes, A and Kon, OM (2014) ESX1-dependent fractalkine mediates chemotaxis and Mycobacterium tuberculosis infection in humans Tuberculosis, 94 (3). pp. 262-270.

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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. © 2014 The Authors.

Item Type: Article
Authors :
NameEmailORCID
Hingley-Wilson, SMs.hingley-wilson@surrey.ac.ukUNSPECIFIED
Connell, DUNSPECIFIEDUNSPECIFIED
Pollock, KUNSPECIFIEDUNSPECIFIED
Grass, LUNSPECIFIEDUNSPECIFIED
Potiphar, LUNSPECIFIEDUNSPECIFIED
Bremang, SUNSPECIFIEDUNSPECIFIED
Lalvani, AUNSPECIFIEDUNSPECIFIED
Hsu, TUNSPECIFIEDUNSPECIFIED
Jacobs Jr, WRUNSPECIFIEDUNSPECIFIED
Tchilian, EUNSPECIFIEDUNSPECIFIED
Sykes, AUNSPECIFIEDUNSPECIFIED
Kon, OMUNSPECIFIEDUNSPECIFIED
Date : 2014
Identification Number : 10.1016/j.tube.2014.01.004
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 10:10
Last Modified : 30 Oct 2017 13:52
URI: http://epubs.surrey.ac.uk/id/eprint/826657

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