18 Cytokine Levels Modulate Innate Immune Responses and Cryptosporidiosis in Mice

• Published in: The Journal of eukaryotic microbiology 2015, Vol.62 (1), p.44-50
• Main Authors: Bedi, Brahmchetna, McNair, Nina N, Förster, Irmgard, Mead, Jan R
• Format: Article
• Language: English
• Subjects: anti-infective properties; blood serum; cathelicidins; cryptosporidiosis; Cryptosporidium parvum; gene expression; genes; innate immunity; interferon-gamma; interleukin-18; intestinal mucosa; messenger RNA; mice; parasite load; protective effect; severe combined immunodeficiency
• ISSN: 1066-5234; 1550-7408

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.