title: Gal-lectin-dependent contact activates the inflammasome by invasive Entamoeba histolytica.
abstract: Entamoeba histolytica (Eh) is an extracellular protozoan parasite of the human colon, which occasionally breaches the intestinal barrier. Eradicating ameba that invades is essential for host survival. A defining but uncharacterized feature of amebic invasion is direct contact between ameba and host cells. This event corresponds with a massive pro-inflammatory response. To date, pathogen recognition receptors (PRRs) that are activated by contact with viable Eh are unknown. Here we show that the innate immune system responds in a qualitatively different way to contact with viable Eh vs. soluble ligands produced by viable or dead ameba. This unique Eh Gal-lectin contact-dependent response in macrophages was mediated by activation of the inflammasome. Soluble native Gal-lectin did not induce inflammasome activation, but was sufficient for transcriptional priming of the inflammasome and non-inflammasome-dependent pro-inflammatory cytokine release. We conclude the inflammasome is a pathogenicity sensor for invasive Eh and identify for the first time a PRR that specifically responds to contact with intact parasites in a manner that accords with scale immune response to parasite invasion.
authors.affiliation: Faculty of Medicine, Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, Gastrointestinal Research Group, University of Calgary, Calgary, Alberta, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Mortimer
authors.affiliation: Faculty of Medicine, Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, Gastrointestinal Research Group, University of Calgary, Calgary, Alberta, Canada.
authors.forename: F
authors.initials: F
authors.lastname: Moreau
authors.affiliation: Faculty of Medicine, Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, Gastrointestinal Research Group, University of Calgary, Calgary, Alberta, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Cornick
authors.affiliation: Faculty of Medicine, Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, Gastrointestinal Research Group, University of Calgary, Calgary, Alberta, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Chadee
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology* / Q000378:metabolism; D020170:Caspase 1 / Q000378:metabolism; D004748:Entamoeba histolytica / Q000502:physiology*; D004749:Entamoebiasis / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology; D000939:Epitopes / Q000276:immunology; D005849:Gerbillinae; D058847:Inflammasomes; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D015800:Protozoan Proteins / Q000276:immunology* / Q000378:metabolism
chemical_list: D000953:Antigens, Protozoan; D000939:Epitopes; D058847:Inflammasomes; D008562:Membrane Glycoproteins; D015800:Protozoan Proteins; D020170:Caspase 1