Intracellular Invasion of Orientia tsutsugamushi Activates Inflammasome in ASC-Dependent Manner

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Intracellular Invasion of Orientia tsutsugamushi Activates Inflammasome in ASC-Dependent Manner

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Title: Intracellular Invasion of Orientia tsutsugamushi Activates Inflammasome in ASC-Dependent Manner
Author: Koo, Jung-Eun; Hong, Hye-Jin; Dearth, Andrea; Koh, Young-Sang; Kobayashi, Koichi S.

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Citation: Koo, Jung-Eun, Hye-Jin Hong, Andrea Dearth, Koichi S. Kobayashi, and Young-Sang Koh. 2012. Intracellular invasion of Orientia tsutsugamushi activates inflammasome in ASC-dependent manner. PLoS ONE 7(6): e39042.
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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.
Published Version: doi:10.1371/journal.pone.0039042
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3377614/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10436328
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