title: Role of Eosinophils and Tumor Necrosis Factor Alpha in Interleukin-25-Mediated Protection from Amebic Colitis.
abstract: The parasiteEntamoeba histolyticais a cause of diarrhea in infants in low-income countries. Previously, it was shown that tumor necrosis factor alpha (TNF-α) production was associated with increased risk ofE. histolyticadiarrhea in children. Interleukin-25 (IL-25) is a cytokine that is produced by intestinal epithelial cells that has a role in maintenance of gut barrier function and inhibition of TNF-α production. IL-25 expression was decreased in humans and in the mouse model of amebic colitis. Repletion of IL-25 blockedE. histolyticainfection and barrier disruption in mice, increased gut eosinophils, and suppressed colonic TNF-α. Depletion of eosinophils with anti-Siglec-F antibody prevented IL-25-mediated protection. In contrast, depletion of TNF-α resulted in resistance to amebic infection. We concluded that IL-25 provides protection from amebiasis, which is dependent upon intestinal eosinophils and suppression of TNF-α.IMPORTANCEThe intestinal epithelial barrier is important for protection from intestinal amebiasis. We discovered that the intestinal epithelial cytokine IL-25 was suppressed during amebic colitis in humans and that protection could be restored in the mouse model by IL-25 administration. IL-25 acted via eosinophils and suppressed TNF-α. This work illustrates a previously unrecognized pathway of innate mucosal immune response.
authors.affiliation: Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA.
authors.forename: Zannatun
authors.initials: Z
authors.lastname: Noor
authors.affiliation: Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA.|AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA.
authors.forename: Mayuresh M
authors.initials: MM
authors.lastname: Abhyankar
authors.affiliation: Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA.
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Burgess
authors.affiliation: Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA.
authors.forename: Erica L
authors.initials: EL
authors.lastname: Buonomo
authors.affiliation: Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA.
authors.forename: Carrie A
authors.identifier: 0000-0002-8225-8261
authors.initials: CA
authors.lastname: Cowardin
authors.affiliation: Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA wap3g@virginia.edu.
authors.forename: William A
authors.initials: WA
authors.lastname: Petri
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004404:Dysentery, Amebic / Q000276:immunology*; D004748:Entamoeba histolytica / Q000276:immunology*; D004804:Eosinophils / Q000276:immunology*; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: C486701:IL25 protein, human; D020381:Interleukin-17; D007378:Interleukins; C442281:Mydgf protein, mouse; D014409:Tumor Necrosis Factor-alpha