University of Surrey, Faculty of Health and Medical Sciences, Guildford, UK.
Immunobiology. 2011 Jan-Feb;216(1-2):152-63. doi: 10.1016/j.imbio.2010.06.004. Epub 2010 Jun 22.
The Major Outer Membrane Protein (MOMP) belongs to the membrane complex of cysteine-rich proteins of Chlamydophila pneumoniae. Although MOMP can elicit strong immune responses it fails to confer long-term protection against infection in animal models. This effect has been attributed, at least in part, to an inadequate induction of protective Th1-mediated immune responses. In an effort to understand the cellular mechanisms associated to the immunomodulatory properties of MOMP we studied the effect of this protein on mouse macrophages and naïve T-lymphocytes. We found that incubation of mouse macrophages with recombinant MOMP (rMOMP) results in an increased secretion of MMP-9 and a down-regulation of MHC class II, CD86 and CD40. This was accompanied by an increase in IL-10 and IFNγ but not in IL-12 secretion. rMOMP induced a down-regulation of the expression of CD69 and CD154 markers by activated CD4(+) T cells, and enhanced the secretion of IL-2 and IL-10 by these cells. Conversely, rMOMP-treated macrophages up-regulated the expression of CD69 but not CD154, inhibited the synthesis of IL-10 and up-regulated the production of IFNγ by activated CD8(+) T cells. Immunization of mice with MOMP induced the synthesis only of MOMP-specific IgG1 but no differences in cytokine profile were observed compared to controls. Our results provide new evidence on the role of MOMP in modulating T cell-mediated immune responses.
主要外膜蛋白(MOMP)属于鹦鹉热衣原体胱氨酸丰富蛋白的膜复合物。虽然 MOMP 可以引起强烈的免疫反应,但它不能在动物模型中提供长期的抗感染保护。这种效应至少部分归因于保护性 Th1 介导的免疫反应诱导不足。为了了解与 MOMP 的免疫调节特性相关的细胞机制,我们研究了该蛋白对小鼠巨噬细胞和幼稚 T 淋巴细胞的影响。我们发现,用重组 MOMP(rMOMP)孵育小鼠巨噬细胞会导致 MMP-9 分泌增加,MHC Ⅱ类、CD86 和 CD40 表达下调。这伴随着 IL-10 和 IFNγ 的增加,但 IL-12 的分泌没有增加。rMOMP 诱导激活的 CD4(+) T 细胞下调 CD69 和 CD154 标志物的表达,并增强这些细胞分泌 IL-2 和 IL-10。相反,rMOMP 处理的巨噬细胞上调 CD69 的表达,但不上调 CD154,抑制 IL-10 的合成,并上调激活的 CD8(+) T 细胞产生 IFNγ。用 MOMP 免疫小鼠仅诱导 MOMP 特异性 IgG1 的合成,但与对照组相比,细胞因子谱没有差异。我们的研究结果为 MOMP 在调节 T 细胞介导的免疫反应中的作用提供了新的证据。