@article{Krishnan:2013:10.1016/j.tube.2013.05.002,
author = {Krishnan, N and Robertson, BD and Thwaites, G},
doi = {10.1016/j.tube.2013.05.002},
journal = {Tuberculosis},
pages = {538--547},
title = {Pathways of IL-1β secretion by macrophages infected with clinical Mycobacterium tuberculosis strains},
url = {http://dx.doi.org/10.1016/j.tube.2013.05.002},
volume = {93},
year = {2013}
}

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TY  - JOUR
AB  - The pro-inflammatory cytokine IL-1β is a key mediator of inflammation and plays an important role in the host resistance to Mycobacterium tuberculosis infections. To date, most studies have examined the mechanisms of IL-1β secretion using laboratory strains of M. tuberculosis and the findings may not be widely applicable to contemporary clinical strains. Here, we investigated the primary pathways of IL-1β secretion in macrophages infected with a panel of 17 clinical M. tuberculosis isolates, representing Euro-American, Indo-Oceanic and East-Asian/Beijing lineages. Our aim was to dissect the pathways involved in M. tuberculosis induced IL-1β secretion and to determine whether they are common to all clinical isolates. We found that the isolates were capable of eliciting variable concentrations of IL-1β from infected murine macrophages, but this phenomenon could not be attributed to differential IL-1β mRNA transcription or pro-IL-1β accumulation. We demonstrate that viable bacteria are required to induce IL-1β secretion from macrophages, but IL-1β secretion was only partially abrogated by caspase-1 inhibition. Almost complete IL-1β secretion inhibition was produced with combined caspase-1 and some serine protease inhibitors. Taken together, these findings demonstrate that clinical strains of M. tuberculosis employ a unique caspase-1 independent pathway to stimulate IL-1β secretion from macrophages.
AU  - Krishnan,N
AU  - Robertson,BD
AU  - Thwaites,G
DO  - 10.1016/j.tube.2013.05.002
EP  - 547
PY  - 2013///
SN  - 1873-281X
SP  - 538
TI  - Pathways of IL-1β secretion by macrophages infected with clinical Mycobacterium tuberculosis strains
T2  - Tuberculosis
UR  - http://dx.doi.org/10.1016/j.tube.2013.05.002
UR  - http://hdl.handle.net/10044/1/41483
VL  - 93
ER  - 

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