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IL ‐18 Cytokine Levels Modulate Innate Immune Responses and Cryptosporidiosis in Mice
Author(s) -
Bedi Brahmchetna,
McNair Ni.,
Förster Irmgard,
Mead Jan R.
Publication year - 2014
Publication title -
journal of eukaryotic microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.067
H-Index - 77
eISSN - 1550-7408
pISSN - 1066-5234
DOI - 10.1111/jeu.12164
Subject(s) - cathelicidin , biology , cryptosporidium parvum , antimicrobial peptides , beta defensin , immune system , cytokine , microbiology and biotechnology , innate immune system , recombinant dna , immunology , antimicrobial , rna , gene , biochemistry
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 (r IL ‐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 r IL ‐18. In addition, C. parvum infection significantly increased m RNA expression levels (> 50 fold) of the alpha defensins, Defa3 and 5, respectively. Interestingly, we also found a decrease in m RNA expression of IL‐33 (a recently identified cytokine in the same family as IL‐18) in the small intestinal tissue from mice treated with r IL ‐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.