The NLRP3 Inflammasome Is a Pathogen Sensor for Invasive via Activation of α5β1 Integrin at the Macrophage-Amebae Intercellular Junction

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Amebiasis caused by the enteric protozoan parasite Entamoeba histolytica is among the three top causes of death from parasitic infections worldwide, as a result of amebic colitis (dysentery) and liver or brain abscess. When Eh invades the intestinal barrier and contacts host tissue there is a profound inflammatory response, which is thought to drive the disease. One of the central outstanding questions has been how the immune response is escalated at sites of invasion. Adherence of the parasite to host cells has long been appreciated in the pathogenesis of amebiasis, but was never considered as a “cue” that host cells use to detect Eh and initiate host defense. Here we introduce the idea, and demonstrate, that an intercellular junction forms between Eh and host cells upon contact that engages the NLRP3 inflammasome. The NLRP3 inflammasome belongs to a group of “danger” sensors that are uniquely designed to rapidly activate highly inflammatory host defenses. In this work, we identified a surface receptor on macrophages that normally functions in adhesion and polarization recognizes a protein on the outer surface of Eh. Intriguingly, Eh also secretes this protein. However, the full activation of the surface receptor leading to inflammasome activation only occurs when the Eh protein is immobilized on the parasite surface. Thus, we uncovered a molecular mechanism though which host cells distinguish direct contact, and therefore recognize parasites that are immediately present in the tissue, to mobilize a highly inflammatory response. We believe this concept is central to understanding the biology of amebiasis.

Vyšlo v časopise: The NLRP3 Inflammasome Is a Pathogen Sensor for Invasive via Activation of α5β1 Integrin at the Macrophage-Amebae Intercellular Junction. PLoS Pathog 11(5): e32767. doi:10.1371/journal.ppat.1004887
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004887

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