A Protective Role for Interleukin 18 in Interferon gamma-Mediated Innate Immunity to Cryptosporidium parvum That Is Independent of Natural Killer Cells

作者：Choudhry Naheed; Petry Franz; van Rooijen Nico; McDonald Vincent^*

来源：Journal of Infectious Diseases, 2012, 206(1): 117-124.

DOI：10.1093/infdis/jis300

Innate immunity against some intracellular parasitic protozoa involves interleukin 18 (IL-18)-mediated interferon. (IFN-gamma) production by natural killer (NK) cells, but the role of IL-18 in innate resistance to Cryptosporidium infection is unknown. Adult Rag2(-/-)gamma c(-/-) mice that lack NK cells, T cells, and B cells demonstrated resistance to Cryptosporidium parvum infection that was IFN-gamma dependent. Treatment with anti-IL-18-neutralizing antibodies resulted in loss of resistance correlating with reduced intestinal IFN-gamma expression. Intestinal mature IL-18 expression increased in vivo during infection and also in the intestinal epithelial cell line CMT-93 following combined IFN-gamma treatment/infection. Peritoneal macrophages produced IFN-gamma 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-gamma expression. These findings provide evidence of an NK cell-independent, IFN-gamma-mediated innate immune pathway against C. parvum in which IL-18 and macrophages play prominent parts.

• 出版日期2012-7-1
• 单位河北医科大学