title: Entamoeba histolytica induces intestinal cathelicidins but is resistant to cathelicidin-mediated killing.
abstract: The enteric protozoan parasite Entamoeba histolytica is the cause of potentially fatal amebic colitis and liver abscesses. E. histolytica trophozoites colonize the colon, where they induce inflammation, penetrate the mucosa, and disrupt the host immune system. The early establishment of E. histolytica in the colon occurs in the presence of antimicrobial human (LL-37) and murine (CRAMP [cathelin-related antimicrobial peptide]) cathelicidins, essential components of the mammalian innate defense system in the intestine. Studying this early step in the pathogenesis of amebic colitis, we demonstrate that E. histolytica trophozoites or their released proteinases, including cysteine proteinase 1 (EhCP1), induce intestinal cathelicidins in human intestinal epithelial cell lines and in a mouse model of amebic colitis. Despite induction, E. histolytica trophozoites were found to be resistant to killing by these antimicrobial peptides, and LL-37 and CRAMP were rapidly cleaved by released amebic cysteine proteases. The cathelicidin fragments however, did maintain their antimicrobial activity against bacteria. Degradation of intestinal cathelicidins is a novel function of E. histolytica cysteine proteinases in the evasion of the innate immune system in the bowel. Thus, early intestinal epithelial colonization of invasive trophozoites involves a complex interplay in which the ultimate outcome of infection depends in part on the balance between degradation of cathelicidins by amebic released cysteine proteinases and upregulation of proinflammatory mediators which trigger the inflammatory response.
authors.affiliation: Department of Pathology, University of California, San Diego School of Medicine, San Diego, CA, USA.
authors.forename: Eduardo R
authors.initials: ER
authors.lastname: Cobo
authors.forename: Chen
authors.initials: C
authors.lastname: He
authors.forename: Ken
authors.initials: K
authors.lastname: Hirata
authors.forename: Grace
authors.initials: G
authors.lastname: Hwang
authors.forename: UyenPhuong
authors.initials: U
authors.lastname: Tran
authors.forename: Lars
authors.initials: L
authors.lastname: Eckmann
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gallo
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Reed
mesh_terms: D000818:Animals; D054804:Cathelicidins / Q000096:biosynthesis* / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival; D057056:Cysteine Proteases / Q000378:metabolism; D004404:Dysentery, Amebic / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D004748:Entamoeba histolytica / Q000201:enzymology / Q000276:immunology* / Q000472:pathogenicity*; D004847:Epithelial Cells / Q000276:immunology / Q000469:parasitology; D006801:Humans; D057131:Immune Evasion; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D059748:Proteolysis
chemical_list: D054804:Cathelicidins; D057056:Cysteine Proteases
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