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Expression of CD1d and Ligand-Induced Cytokine Production Are Tissue Specific in Mucosal Epithelia of the Human Lower Reproductive Tract

机译:CD1d和配体诱导的细胞因子生产的表达是人类下生殖道粘膜上皮组织特异性的。

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Mucosal epithelia of the human lower reproductive tract (vagina, cervix, and penile urethra) are exposed to sexually transmitted microbes, including Chlamydia trachomatis. The in vivo susceptibility of each tissue type to infection with C. trachomatis is quite distinct. CD1d is expressed on the surface of antigen-presenting cells, including mucosal epithelial cells, and interacts specifically with invariant NKT cells. Invariant NKT cells play a role in both innate and adaptive immune responses to microbes. Here we assessed CD1d expression in normal reproductive tissues by using immunohistochemistry. Immortalized epithelial cell lines from the human lower reproductive tract (vagina, endocervix, and penile urethra) were examined for CD1d expression and for ligand-induced cytokine production induced by CD1d cross-linking. CD1d expression in normal tissue was strong in the vagina but weak in the endocervix and penile urethra. Gamma interferon exposure induced CD1d transcription in all of the cell types studied, with the strongest induction in vaginal cells. Flow cytometry revealed cell surface expression of CD1d in vaginal and penile urethral epithelial cells but not in endocervical cells. Ligation of surface-expressed CD1d by monoclonal antibody cross-linking promoted interleukin-12 (IL-12) and IL-15, but not IL-10, production in vaginal and penile urethral cells. No induction was demonstrated in endocervical cells. CD1d-mediated cytokine production in penile urethral cells was abrogated by C. trachomatis infection. Basal deficiency in CD1d-mediated immune responsiveness may result in susceptibility to sexually transmitted agents. Decreased CD1d-mediated signaling may help C. trachomatis evade detection by innate immune cells.
机译:人类下生殖道(阴道,子宫颈和阴茎尿道)的粘膜上皮暴露于包括沙眼衣原体在内的性传播微生物。每种组织类型对 C感染的体内敏感性。沙眼很明显。 CD1d在包括黏膜上皮细胞在内的抗原呈递细胞的表面表达,并与不变的NKT细胞特异性相互作用。不变的NKT细胞在对微生物的天然免疫和适应性免疫反应中均发挥作用。在这里,我们通过免疫组织化学评估了正常生殖组织中CD1d的表达。检查了人类下生殖道(阴道,子宫颈和阴茎尿道)永生化的上皮细胞系的CD1d表达以及由CD1d交联诱导的配体诱导的细胞因子生成。正常组织中CD1d的表达在阴道中很强,但在子宫颈内膜和阴茎尿道中很弱。 γ干扰素暴露可在所有研究的细胞类型中诱导CD1d转录,而在阴道细胞中的诱导作用最强。流式细胞仪揭示了CD1d在阴道和阴茎尿道上皮细胞中的细胞表面表达,但在子宫颈内膜细胞中没有。通过单克隆抗体交联的表面表达的CD1d的连接促进了阴道和阴茎尿道细胞中白介素12(IL-12)和IL-15的产生,但没有促进IL-10的产生。在宫颈内膜细胞中未显示出诱导作用。阴茎尿道细胞中CD1d介导的细胞因子的产生被 C废除。沙眼炎感染。 CD1d介导的免疫反应能力的基础不足可能导致对性传播药物的敏感性。 CD1d介导的信号传导减少可能有助于C。沙眼逃避了先天免疫细胞的检测。

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