TLR9-Dependent Induction of Intestinal α-Defensins by Toxoplasma gondii
TLR9-Dependent Induction of Intestinal α-Defensins by Toxoplasma gondii
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DOI：
10.4049/jimmunol.0901642
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发表时间：
2010-06-15
影响因子：
4.4
通讯作者：
Buzoni-Gatel, Dominique
中科院分区：
文献类型：
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作者：
Foureau, David M.;Mielcarz, Daniel W.;Buzoni-Gatel, Dominique
α-防御素（或隐蛋白 [Crps]）是一组抗菌肽，作为小肠潘氏细胞 (PC) 分泌颗粒的成分而产生。合成激动剂在体内连接 TLR9 会导致 PC 脱颗粒，尽管发生这种情况的机制仍不确定。在本报告中，我们研究了 TLR9 依赖性机制，由寄生虫弓形虫触发，诱导管腔中 Crp 释放。用弓形虫口服 C57BL/6J (B6) 野生型 (WT) 小鼠可诱导 TLR9 mRNA 上调，并与 I 型 IFN mRNA 表达显着增加相关。 B6 WT 小鼠口服攻击后，PC 分泌颗粒被释放，纯化的上皮细胞的 Crp-3/-5 mRNA 表达增加。尽管 PC 在受感染的 B6 TLR9(-/-) 小鼠中未能脱粒，但腹膜内注射。单独注射小鼠 IFN-β 导致 B6 WT 和 TLR9(-/-) 小鼠中 Crp-3/-5 mRNA 上调。此外，在缺乏功能性I型IFN受体的B6 IFNAR(-/-)小鼠中，响应弓形虫感染而对Crp mRNA表达的调节被取消。总而言之，这些数据表明弓形虫通过 TLR9 依赖性 I 型 IFN 的产生来诱导 PC 产生和释放 Crp-3/-5。 Crps 对弓形虫的直接作用有限，但可能通过促进针对寄生虫的保护性 Th1 反应的启动，间接影响弓形虫入侵的早期控制。免疫学杂志，2010，184：7022-7029。
alpha-Defensins (or Cryptdins [Crps]) are a group of antimicrobial peptides produced as a component of Paneth cell (PC) secretory granules in the small intestine. In vivo ligation of TLR9 by synthetic agonists leads to PC degranulation, although the mechanism by which this occurs remains uncertain. In this report, we investigated TLR9-dependent mechanisms, triggered by the parasite Toxoplasma gondii, inducing Crp release in the lumen. Oral challenge of C57BL/6J (B6) wild-type (WT) mice with T. gondii induced TLR9 mRNA upregulation associated with a marked increase of type I IFN mRNA expression. PC secretory granules were released, and Crp-3/-5 mRNA expression by purified epithelial cells was increased following oral challenge of B6 WT mice. Although PCs failed to degranulate in infected B6 TLR9(-/-) mice, i.p. injection of mouse IFN-beta alone led to Crp-3/-5 mRNA upregulation in B6 WT and TLR9(-/-) mice. In addition, modulation of Crp mRNA expression in response to T. gondii infection was abrogated in B6 IFNAR(-/-) mice, which lack a functional type I IFN receptor. Taken together, these data demonstrate that T. gondii induces Crp-3/-5 production and release by PCs via a TLR9-dependent production of type I IFNs. Crps have a limited direct effect against T. gondii but may indirectly affect the early control of T. gondii invasiveness by promoting the initiation of a protective Th1 response against the parasite. The Journal of Immunology, 2010, 184: 7022-7029.