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PLoS One. 2012;7(6):e39042. doi: 10.1371/journal.pone.0039042. Epub 2012 Jun 18.

Intracellular invasion of Orientia tsutsugamushi activates inflammasome in asc-dependent manner.

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1
Department of Microbiology and Immunology, Brain Korea 21 Program, Jeju National University School of Medicine, Jeju, Jeju-Do, South Korea.

Abstract

Orientia tsutsugamushi, a causative agent of scrub typhus, is an obligate intracellular bacterium, which escapes from the endo/phagosome and replicates in the host cytoplasm. O. tsutsugamushi infection induces production of pro-inflammatory mediators including interleukin-1β (IL-1β), which is secreted mainly from macrophages upon cytosolic stimuli by activating cysteine protease caspase-1 within a complex called the inflammasome, and is a key player in initiating and maintaining the inflammatory response. However, the mechanism for IL-1β maturation upon O. tsutsugamushi infection has not been identified. In this study, we show that IL-1 receptor signaling is required for efficient host protection from O. tsutsugamushi infection. Live Orientia, but not heat- or UV-inactivated Orientia, activates the inflammasome through active bacterial uptake and endo/phagosomal maturation. Furthermore, Orientia-stimulated secretion of IL-1β and activation of caspase-1 are ASC- and caspase-1- dependent since IL-1β production was impaired in Asc- and caspase-1-deficient macrophages but not in Nlrp3-, Nlrc4- and Aim2-deficient macrophages. Therefore, live O. tsutsugamushi triggers ASC inflammasome activation leading to IL-1β production, which is a critical innate immune response for effective host defense.

PMID:
22723924
PMCID:
PMC3377614
DOI:
10.1371/journal.pone.0039042
[Indexed for MEDLINE]
Free PMC Article
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