The IL-6 response to Chlamydia from primary reproductive epithelial cells is highly variable and may be involved in differential susceptibility to the immunopathological consequences of chlamydial infection.

The IL-6 response to Chlamydia from primary reproductive epithelial cells is highly variable and may be involved in differential susceptibility to the immunopathological consequences of chlamydial infection.
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DOI:
10.1186/1471-2172-14-50
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发表时间:
2013-11-15
期刊:
影响因子:
3
通讯作者:
Huston WM
Huston WM
中科院分区:
医学4区
文献类型:
--
作者:
Cunningham K;Stansfield SH;Patel P;Menon S;Kienzle V;Allan JA;Huston WM

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沙眼衣原体感染会导致一些妇女的生殖损害。参与这种免疫病理学的过程和因素还不清楚。本研究旨在研究衣原体应激反应蛋白酶和衣原体感染的主要人类细胞反应的作用,以进一步确定严重疾病后遗症中涉及的免疫过程。实验室细胞培养物和原代人类生殖上皮培养物产生IL-6,以响应衣原体应激反应蛋白酶(CtHtrA和CtTsp)、UV灭活衣原体和活衣原体。IL-6反应的幅度在不同的原代人类生殖培养物中变化很大(高达1000 pg ml-1)。因此,生殖上皮细胞产生不同水平的IL-6可能是疾病结局的决定因素。有趣的是,与THP-1细胞或自体原代人PBMC的共培养模型通常导致IL-6水平增加,除了在活衣原体的情况下,其中IL-6水平与仅上皮细胞培养物相比降低,表明该途径可能能够被活衣原体调节。PBMC对应激反应蛋白酶(CtTsp和CtHtrA)的反应在不同的参与者队列中没有显著差异。因此,这些蛋白酶可能具有保守的先天PAMP。MAP激酶似乎参与了从人细胞诱导IL-6。最后,我们还证明了IL-6诱导这些蛋白质和衣原体从小鼠原代生殖细胞培养物(BALB/C小鼠)和小鼠实验室细胞模型。我们已经证明,IL-6可能是人类衣原体疾病结局的关键因素,因为原代人类生殖上皮细胞培养显示IL-6对衣原体或衣原体蛋白的反应存在相当大的差异,并且在共培养期间存在活衣原体(但不是UV杀死的)导致IL-6反应降低,表明这种反应可能被生物体的存在所缓和。
Chlamydia trachomatis infection results in reproductive damage in some women. The process and factors involved in this immunopathology are not well understood. This study aimed to investigate the role of primary human cellular responses to chlamydial stress response proteases and chlamydial infection to further identify the immune processes involved in serious disease sequelae. Laboratory cell cultures and primary human reproductive epithelial cultures produced IL-6 in response to chlamydial stress response proteases (CtHtrA and CtTsp), UV inactivated Chlamydia, and live Chlamydia. The magnitude of the IL-6 response varied considerably (up to 1000 pg ml-1) across different primary human reproductive cultures. Thus different levels of IL-6 production by reproductive epithelia may be a determinant in disease outcome. Interestingly, co-culture models with either THP-1 cells or autologous primary human PBMC generally resulted in increased levels of IL-6, except in the case of live Chlamydia where the level of IL-6 was decreased compared to the epithelial cell culture only, suggesting this pathway may be able to be modulated by live Chlamydia. PBMC responses to the stress response proteases (CtTsp and CtHtrA) did not significantly vary for the different participant cohorts. Therefore, these proteases may possess conserved innate PAMPs. MAP kinases appeared to be involved in this IL-6 induction from human cells. Finally, we also demonstrated that IL-6 was induced by these proteins and Chlamydia from mouse primary reproductive cell cultures (BALB/C mice) and mouse laboratory cell models. We have demonstrated that IL-6 may be a key factor for the chlamydial disease outcome in humans, given that primary human reproductive epithelial cell culture showed considerable variation in IL-6 response to Chlamydia or chlamydial proteins, and that the presence of live Chlamydia (but not UV killed) during co-culture resulted in a reduced IL-6 response suggesting this response may be moderated by the presence of the organism.
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发表时间: 1997-01-01
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作者:
Castelbaum, AJ;Ying, L;Lessey, BA
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