Derbigny Wilbert A, Kerr Micah S, Johnson Raymond M
Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
J Immunol. 2005 Nov 1;175(9):6065-75. doi: 10.4049/jimmunol.175.9.6065.
Chlamydia trachomatis is the most common bacterial sexually transmitted disease in the United States and a major cause of female infertility due to infection-induced Fallopian tube scarring. Epithelial cells are likely central to host defense and pathophysiology as they are the principal cell type productively infected by C. trachomatis. We generated cloned murine oviduct epithelial cell lines without viral or chemical transformation to investigate the role of the TLRs and cytosolic nucleotide binding site/leucine-rich repeat proteins Nod1 and Nod2 in epithelial responses to Chlamydia muridarum infection. RT-PCR assays detected mRNA for TLR2 (TLRs 1 and 6), TLR3, and TLR5. No mRNA was detected for TLRs 4, 7, 8, and 9. Messenger RNAs for Nod1 and Nod2 were present in the epithelial cell lines. Oviduct epithelial cell lines infected with C. muridarum or exposed to the TLR2 agonist peptidoglycan secreted representative acute phase cytokines IL-6 and GM-CSF in a MyD88-dependent fashion. Infected epithelial cell lines secreted the immunomodulatory cytokine IFN-beta, even though C. muridarum does not have a clear pathogen-associated molecular pattern (PAMP) for triggering IFN-beta transcription. The oviduct epithelial lines did not secrete IFN-beta in response to the TLR2 agonist peptidoglycan or to the TLR3 agonist poly(I:C). Our data identify TLR2 as the principal TLR responsible for secretion of acute phase cytokines by C. muridarum-infected oviduct epithelial cell lines. The pattern recognition molecule responsible for infection-induced IFN-beta secretion by oviduct epithelial cells remains to be determined.
沙眼衣原体是美国最常见的细菌性性传播疾病，也是因感染导致输卵管瘢痕形成进而造成女性不孕的主要原因。上皮细胞可能是宿主防御和病理生理学的核心，因为它们是被沙眼衣原体有效感染的主要细胞类型。我们构建了未经病毒或化学转化的克隆鼠输卵管上皮细胞系，以研究Toll样受体（TLRs）以及胞质核苷酸结合位点/富含亮氨酸重复序列蛋白Nod1和Nod2在输卵管上皮细胞对鼠沙眼衣原体感染反应中的作用。逆转录聚合酶链反应（RT-PCR）检测到TLR2（TLR1和TLR6）、TLR3和TLR5的信使核糖核酸（mRNA）。未检测到TLR4、TLR7、TLR8和TLR9的mRNA。上皮细胞系中存在Nod1和Nod2的信使核糖核酸。感染鼠沙眼衣原体或暴露于TLR2激动剂肽聚糖的输卵管上皮细胞系以髓样分化因子88（MyD88）依赖的方式分泌代表性的急性期细胞因子白细胞介素-6（IL-6）和粒细胞-巨噬细胞集落刺激因子（GM-CSF）。尽管鼠沙眼衣原体没有明确的病原体相关分子模式（PAMP）来触发干扰素-β（IFN-β）转录，但受感染的上皮细胞系仍分泌免疫调节细胞因子IFN-β。输卵管上皮细胞系对TLR2激动剂肽聚糖或TLR3激动剂聚肌苷酸-聚胞苷酸（poly(I:C)）无反应，不分泌IFN-β。我们的数据表明，TLR2是鼠沙眼衣原体感染的输卵管上皮细胞系分泌急性期细胞因子的主要Toll样受体。负责输卵管上皮细胞因感染而分泌IFN-β的模式识别分子仍有待确定。
