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首页> 外文期刊>BMC Microbiology >Intracellular Mycoplasma genitalium infection of human vaginal and cervical epithelial cells elicits distinct patterns of inflammatory cytokine secretion and provides a possible survival niche against macrophage-mediated killing
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Intracellular Mycoplasma genitalium infection of human vaginal and cervical epithelial cells elicits distinct patterns of inflammatory cytokine secretion and provides a possible survival niche against macrophage-mediated killing

机译：人阴道和宫颈上皮细胞的细胞内支原体生殖道感染引起炎症细胞因子分泌的不同模式，并提供了可能的生存位以对抗巨噬细胞介导的杀伤

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Mycoplasma genitalium is an emerging sexually transmitted pathogen that has been associated with significant reproductive tract inflammatory syndromes in women. In addition, the strong association between severity of M. genitalium infection and Human Immunodeficiency Virus type 1 (HIV-1) shedding from the cervix suggests that innate responses to M. genitalium may influence pathogenesis of other sexually transmitted infections. Epithelial cells (ECs) of the reproductive mucosa are the first cells contacted by sexually transmitted pathogens. Therefore, we first characterized the dynamics of intracellular and extracellular localization and resultant innate immune responses from human vaginal, ecto- and endocervical ECs to M. genitalium type strain G37 and a low-pass contemporary isolate, M2300. Both M. genitalium strains rapidly attached to vaginal and cervical ECs by 2 h post-infection (PI). By 3 h PI, M. genitalium organisms also were found in intracellular membrane-bound vacuoles of which approximately 60% were adjacent to the nucleus. Egress of M. genitalium from infected ECs into the culture supernatant was observed but, after invasion, viable intracellular titers were significantly higher than extracellular titers at 24 and 48 h PI. All of the tested cell types responded by secreting significant levels of pro-inflammatory cytokines and chemokines in a pattern consistent with recruitment and stimulation of monocytes and macrophages. Based on the elaborated cytokines, we next investigated the cellular interaction of M. genitalium with human monocyte-derived macrophages and characterized the resultant cytokine responses. Macrophages rapidly phagocytosed M. genitalium resulting in a loss of bacterial viability and a potent pro-inflammatory response that included significant secretion of IL-6 and other cytokines associated with enhanced HIV-1 replication. The macrophage-stimulating capacity of M. genitalium was independent of bacterial viability but was sensitive to heat denaturation and proteinase-K digestion suggesting that M. genitalium protein components are the predominant mediators of inflammation. Collectively, the data indicated that human genital ECs were susceptible and immunologically responsive to M. genitalium infection that likely induced cellular immune responses. Although macrophage phagocytosis was an effective method for M. genitalium killing, intracellular localization within vaginal and cervical ECs may provide M. genitalium a survival niche and protection from cellular immune responses thereby facilitating the establishment and maintenance of reproductive tract infection.
机译：生殖道支原体是一种新兴的性传播病原体，已与妇女严重的生殖道炎性综合征相关。此外，生殖器支原体感染的严重性与子宫颈脱落的人类免疫缺陷病毒1型（HIV-1）之间的强烈关联表明对生殖器支原体的先天反应可能会影响其他性传播感染的发病机制。生殖粘膜的上皮细胞（EC）是性传播病原体接触的第一批细胞。因此，我们首先表征了细胞内和细胞外定位的动态以及由此产生的人类阴道，直肠和宫颈内膜内皮细胞对生殖器支原体型菌株G37和低通当代分离株M2300的固有免疫反应。两种生殖生殖支原体菌株均在感染后2小时迅速附着在阴道和宫颈EC上。到PI 3小时后，在细胞内膜结合液泡中也发现了生殖器支原体微生物，其中约60％与细胞核相邻。观察到生殖支原体从被感染的EC流出到培养上清液中，但是在侵袭后，存活的细胞内滴度在PI 24和48 h显着高于细胞外滴度。所有测试的细胞类型均以与单核细胞和巨噬细胞募集和刺激一致的方式分泌大量促炎性细胞因子和趋化因子来响应。基于精心设计的细胞因子，我们接下来研究了生殖器支原体与人单核细胞衍生的巨噬细胞的细胞相互作用，并表征了所产生的细胞因子反应。巨噬细胞迅速吞噬了生殖器支原体，导致细菌活力丧失和强烈的促炎反应，包括大量分泌IL-6和其他与HIV-1复制增强有关的细胞因子。生殖器支原体的巨噬细胞刺激能力与细菌生存力无关，但对热变性和蛋白酶K消化敏感，表明生殖器支原体的蛋白质成分是炎症的主要介质。总体而言，数据表明，人类生殖器EC对生殖器支原体感染很敏感并具有免疫反应，而生殖支原体可能诱发细胞免疫反应。尽管巨噬细胞吞噬作用是杀死生殖器支原体的有效方法，但阴道和宫颈EC内的细胞内定位可为生殖器支原体提供生存生存的机会并保护其免受细胞免疫应答，从而促进生殖道感染的建立和维持。

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