ESX1-dependent fractalkine mediates chemotaxis and Mycobacterium tuberculosis infection in humans.
Bottom Line: 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).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.
Affiliation: Tuberculosis Research Centre, Department of Respiratory Medicine, National Heart and Lung Institute, Imperial College London, London W2 1PG, United Kingdom. Electronic address: firstname.lastname@example.org.Show MeSH
Related in: MedlinePlus
Mentions: Secretion of all of the innate cytokines measured in response to infection with Mtb was similar to that with infection with the Mtb ΔESX1 mutant (Figure 1a–f), with the exception of the chemokine fractalkine (Figure 2a, P = 0.041). Therefore, uniquely among the panel of chemokines and cytokines evaluated, fractalkine induction at 24 h post-infection in Mtb-infected THP-1 cells is ESX1-mediated. This difference was also observed at 48 h post-infection (data not shown) but in both cases was only observed in resting macrophages, the suggested preferred interstitial niche of the tubercle bacillus  and was not seen in cells activated by the Th1 cytokine interferon-γ (IFN-γ; Figure 2b).
Affiliation: Tuberculosis Research Centre, Department of Respiratory Medicine, National Heart and Lung Institute, Imperial College London, London W2 1PG, United Kingdom. Electronic address: email@example.com.