title: IL-18 cytokine levels modulate innate immune responses and cryptosporidiosis in mice.
abstract: IL-18 is known to play a key role limiting Cryptosporidium parvum infection. In this study, we show that IL-18 depletion in SCID mice significantly exacerbates C. parvum infection, whereas, treatment with recombinant IL-18 (rIL-18), significantly decreases the parasite load, as compared to controls. Increases in serum IFN-γ levels as well as the up-regulation of the antimicrobial peptides, cathelicidin antimicrobial peptide and beta defensin 3 (Defb3) were observed in the intestinal mucosa of mice treated with rIL-18. In addition, C. parvum infection significantly increased mRNA expression levels (> 50 fold) of the alpha defensins, Defa3 and 5, respectively. Interestingly, we also found a decrease in mRNA expression of IL-33 (a recently identified cytokine in the same family as IL-18) in the small intestinal tissue from mice treated with rIL-18. In comparison, the respective genes were induced by IL-18 depletion. Our findings suggest that IL-18 can mediate its protective effects via different routes such as IFN-γ induction or by directly stimulating intestinal epithelial cells to increase antimicrobial activity.
authors.affiliation: Atlanta VA Medical Center, Decatur, Georgia, USA; Department of Pediatrics, Emory University, Atlanta, Georgia, USA.
authors.forename: Brahmchetna
authors.initials: B
authors.lastname: Bedi
authors.forename: Nina N
authors.initials: NN
authors.lastname: McNair
authors.forename: Irmgard
authors.initials: I
authors.lastname: Förster
authors.forename: Jan R
authors.initials: JR
authors.lastname: Mead
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins / Q000819:agonists / Q000235:genetics / Q000276:immunology; D003457:Cryptosporidiosis / Q000188:drug therapy* / Q000276:immunology / Q000469:parasitology; D016785:Cryptosporidium parvum / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation; D007113:Immunity, Innate / Q000187:drug effects*; D018928:Immunity, Mucosal / Q000187:drug effects*; D007371:Interferon-gamma / Q000819:agonists / Q000235:genetics / Q000276:immunology; D020382:Interleukin-18 / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D000067596:Interleukin-33 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology / Q000469:parasitology; D051379:Mice; D016513:Mice, SCID; D059208:Parasite Load; D012333:RNA, Messenger / Q000819:agonists / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D015398:Signal Transduction; D023084:alpha-Defensins / Q000819:agonists / Q000235:genetics / Q000276:immunology; D023083:beta-Defensins / Q000819:agonists / Q000235:genetics / Q000276:immunology
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; C506535:Il33 protein, mouse; D020382:Interleukin-18; D000067596:Interleukin-33; D012333:RNA, Messenger; D011994:Recombinant Proteins; D023084:alpha-Defensins; D023083:beta-Defensins; D007371:Interferon-gamma
keywords: Antimicrobial peptide; cryptosporidium; immunology; intestinal; opportunistic