IL-18 Cytokine Levels Modulate Innate Immune Responses and Cryptosporidiosis in Mice
IL-18 Cytokine Levels Modulate Innate Immune Responses and Cryptosporidiosis in Mice
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DOI：
10.1111/jeu.12164
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发表时间：
2015-01-01
影响因子：
2.2
通讯作者：
Mead, Jan R.
中科院分区：
文献类型：
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作者：
Bedi, Brahmchetna;McNair, Nina N.;Mead, Jan R.
已知IL-18在限制微小隐孢子虫感染中起关键作用。在这项研究中，我们表明，IL-18在SCID小鼠中的耗竭显著加重了C。与对照相比，用重组IL-18（rIL-18）处理显著降低寄生虫负荷。在用rIL-18处理的小鼠的肠粘膜中观察到血清IFN-γ水平的增加以及抗菌肽、抗菌肽和β防御素3（Defb 3）的上调。此外，C.细小病毒感染显著增加了α防御素Defa 3和Defa 5的mRNA表达水平（>50倍）。有趣的是，我们还发现用rIL-18处理的小鼠的小肠组织中IL-33（与IL-18在同一家族中的最近鉴定的细胞因子）的mRNA表达降低。相比之下，各个基因由IL-18消耗诱导。我们的研究结果表明，IL-18可以介导其保护作用，通过不同的途径，如IFN-诱导或直接刺激肠上皮细胞，以增加抗菌活性。
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- 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- induction or by directly stimulating intestinal epithelial cells to increase antimicrobial activity.