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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.

Original publication




Journal article


Tuberculosis (Edinb)

Publication Date





538 - 547


Caspase-1, Interleukin-1β, Macrophages, Mycobacteria, Serine proteases, Animals, Apoptosis, Caspase 1, Cells, Cultured, Enzyme Activation, Female, Genotype, Interleukin-1beta, Macrophages, Mice, Mice, Inbred BALB C, Mycobacterium tuberculosis, RNA, Messenger, Serine Proteinase Inhibitors, Signal Transduction, Species Specificity, Tuberculosis, Virulence