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

SummaryMycobacterium 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

The impact of UK green power marketing within a liberalised European electricity supply industry

SIGLEAvailable from British Library Document Supply Centre- DSC:DXN058052 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

A feminist approach to citizenship

Digitised version produced by the EUI Library and made available online in 2020

Example of a 2D-DIGE image (pI 6–9) depicting differences in protein abundance between sarcoidosis and healthy control spleen tissue.

<p>Example of a 2D-DIGE image (pI 6–9) depicting differences in protein abundance between sarcoidosis and healthy control spleen tissue.</p

Partial Least Squares is used to create a linear regression model to accurately discriminate between sarcoidosis and tuberculosis sera.

<p>Partial Least Squares is used to create a linear regression model to accurately discriminate between sarcoidosis and tuberculosis sera.</p

BAL and serum cytokine levels in pulmonary sarcoidosis, pulmonary tuberculosis and healthy volunteers with Bonferroni-adjusted p-values for each of the possible comparisons.

<p>BAL and serum cytokine levels in pulmonary sarcoidosis, pulmonary tuberculosis and healthy volunteers with Bonferroni-adjusted p-values for each of the possible comparisons.</p

Cytokine profiles in the BAL of pulmonary sarcoidosis, pulmonary tuberculosis and health volunteers.

<p>(A) BAL cytokine profile, (B) BAL levels of TNFα and (C) BAL levels of IL-13.</p

BAL: serum cytokine ratios in different conditions.

<p>(A) BAL: serum cytokine ratios seen in pulmonary sarcoidosis and pulmonary tuberculosis, (B) BAL and serum levels of IL-4 in pulmonary sarcoidosis, (C) BAL and serum levels of IL-4 in pulmonary tuberculosis, (D) BAL and serum levels of IL-4 in healthy volunteers and (E) matched BAL and serum levels of IL-4 in pulmonary sarcoidosis.</p