title: A protective role for interleukin 18 in interferon γ-mediated innate immunity to Cryptosporidium parvum that is independent of natural killer cells.
abstract: Innate immunity against some intracellular parasitic protozoa involves interleukin 18 (IL-18)-mediated interferon γ (IFN-γ) production by natural killer (NK) cells, but the role of IL-18 in innate resistance to Cryptosporidium infection is unknown. Adult Rag2(-/-)γc(-/-) mice that lack NK cells, T cells, and B cells demonstrated resistance to Cryptosporidium parvum infection that was IFN-γ dependent. Treatment with anti-IL-18-neutralizing antibodies resulted in loss of resistance correlating with reduced intestinal IFN-γ expression. Intestinal mature IL-18 expression increased in vivo during infection and also in the intestinal epithelial cell line CMT-93 following combined IFN-γ treatment/infection. Peritoneal macrophages produced IFN-γ when stimulated with IL-18 combined with interleukin 12, and the latter was expressed in vivo during infection. Macrophage depletion in infected mice caused a rapid growth of infection with no increase in IFN-γ expression. These findings provide evidence of an NK cell-independent, IFN-γ-mediated innate immune pathway against C. parvum in which IL-18 and macrophages play prominent parts.
authors.affiliation: Barts and the London School of Medicine and Dentistry, Blizard Institute of Cell and Molecular Science,  Centre for Digestive Diseases, Queen Mary College University of London,  United Kingdom.
authors.forename: Naheed
authors.initials: N
authors.lastname: Choudhry
authors.forename: Franz
authors.initials: F
authors.lastname: Petry
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.forename: Vincent
authors.initials: V
authors.lastname: McDonald
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016785:Cryptosporidium parvum / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology*; D018664:Interleukin-12 / Q000276:immunology; D020382:Interleukin-18 / Q000276:immunology*; D007422:Intestines / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000276:immunology; D013154:Spleen / Q000276:immunology
chemical_list: D020382:Interleukin-18; D012333:RNA, Messenger; D018664:Interleukin-12; D007371:Interferon-gamma