title: Entamoeba histolytica-Encoded Homolog of Macrophage Migration Inhibitory Factor Contributes to Mucosal Inflammation during Amebic Colitis.
abstract: Understanding the mechanisms by which Entamoeba histolytica drives gut inflammation is critical for the development of improved preventive and therapeutic strategies. E. histolytica encodes a homolog of the human cytokine macrophage migration inhibitory factor (MIF). Here, we investigated the role of E. histolytica MIF (EhMIF) during infection. We found that the concentration of fecal EhMIF correlated with the level of intestinal inflammation in persons with intestinal amebiasis. Mice treated with antibodies that specifically block EhMIF had reduced chemokine expression and neutrophil infiltration in the mucosa. In addition to antibody-mediated neutralization, we used a genetic approach to test the effect of EhMIF on mucosal inflammation. Mice infected with parasites overexpressing EhMIF had increased chemokine expression, neutrophil influx, and mucosal damage. Together, these results uncover a specific parasite protein that increases mucosal inflammation, expands our knowledge of host-parasite interaction during amebic colitis, and highlights a potential immunomodulatory target.
authors.affiliation: Department of Medicine, University of Virginia Health System, Charlottesville.
authors.forename: Renay
authors.initials: R
authors.lastname: Ngobeni
authors.affiliation: Department of Medicine, University of Virginia Health System, Charlottesville.
authors.forename: Mayuresh M
authors.initials: MM
authors.lastname: Abhyankar
authors.affiliation: Department of Medicine, University of Virginia Health System, Charlottesville.
authors.forename: Nona M
authors.initials: NM
authors.lastname: Jiang
authors.affiliation: Department of Medicine, University of Virginia Health System, Charlottesville.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Farr
authors.affiliation: Department of Microbiology, University of Venda, Limpopo Province, South Africa; and.
authors.forename: Amidou
authors.initials: A
authors.lastname: Samie
authors.affiliation: International Centre for Diarrheal Disease Research, Dhaka, Bangladesh.
authors.forename: Rashidul
authors.initials: R
authors.lastname: Haque
authors.affiliation: Department of Medicine, University of Virginia Health System, Charlottesville.
authors.forename: Shannon N
authors.initials: SN
authors.lastname: Moonah
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D018938:Caco-2 Cells; D018929:Cell Culture Techniques; D002675:Child, Preschool; D004404:Dysentery, Amebic / Q000188:drug therapy / Q000473:pathology*; D004748:Entamoeba histolytica / Q000187:drug effects; D005243:Feces / Q000737:chemistry; D006790:Host-Parasite Interactions; D006801:Humans; D007413:Intestinal Mucosa / Q000469:parasitology / Q000473:pathology; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D019138:Antibodies, Blocking; D008263:Macrophage Migration-Inhibitory Factors; D015800:Protozoan Proteins
keywords: Chemokines; Entamoeba histolytica; colitis; diarrhea; host–parasite interaction; macrophage migration inhibitory factor; mucosal inflammation; neutrophils.