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• W1518556167 endingPage "e1004887" @default.
• W1518556167 startingPage "e1004887" @default.
• W1518556167 abstract "Entamoeba histolytica (Eh) is an extracellular protozoan parasite of humans that invades the colon to cause life-threatening intestinal and extra-intestinal amebiasis. Colonized Eh is asymptomatic, however, when trophozoites adhere to host cells there is a considerable inflammatory response that is critical in the pathogenesis of amebiasis. The host and/or parasite factors that trigger the inflammatory response to invading Eh are not well understood. We recently identified that Eh adherence to macrophages induces inflammasome activation and in the present study we sought to determine the molecular events upon contact that coordinates this response. Here we report that Eh contact-dependent activation of α5β1 integrin is critical for activation of the NLRP3 inflammasome. Eh-macrophage contact triggered recruitment of α5β1 integrin and NLRP3 into the intercellular junction, where α5β1 integrin underwent activation by an integrin-binding cysteine protease on the parasite surface, termed EhCP5. As a result of its activation, α5β1 integrin induced ATP release into the extracellular space through opening of pannexin-1 channels that signalled through P2X7 receptors to deliver a critical co-stimulatory signal that activated the NLRP3 inflammasome. Both the cysteine protease activity and integrin-binding domain of EhCP5 were required to trigger α5β1 integrin that led to ATP release and NLRP3 inflammasome activation. These findings reveal engagement of α5β1 integrin across the parasite-host junction is a key regulatory step that initiates robust inflammatory responses to Eh. We propose that α5β1 integrin distinguishes Eh direct contact and functions with NLRP3 as pathogenicity sensor for invasive Eh infection." @default.
• W1518556167 created "2016-06-24" @default.
• W1518556167 creator A5011379958 @default.
• W1518556167 creator A5062055649 @default.
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• W1518556167 date "2015-05-08" @default.
• W1518556167 modified "2023-09-27" @default.
• W1518556167 title "The NLRP3 Inflammasome Is a Pathogen Sensor for Invasive Entamoeba histolytica via Activation of α5β1 Integrin at the Macrophage-Amebae Intercellular Junction" @default.
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• W1518556167 doi "https://doi.org/10.1371/journal.ppat.1004887" @default.
• W1518556167 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4425650" @default.
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• W1518556167 hasPublicationYear "2015" @default.
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