Trichomonas vaginalis Lipophosphoglycan Exploits Binding to Galectin-1 and -3 to Modulate Epithelial Immunity.
Trichomonas vaginalis Lipophosphoglycan Exploits Binding to Galectin-1 and -3 to Modulate Epithelial Immunity.
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DOI：
10.1074/jbc.m115.651497
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发表时间：
2016-01-08
期刊：
影响因子：
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通讯作者：
Singh BN
中科院分区：
文献类型：
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作者：
Fichorova RN;Yamamoto HS;Fashemi T;Foley E;Ryan S;Beatty N;Dawood H;Hayes GR;St-Pierre G;Sato S;Singh BN
滴虫病是由嗜阴道原虫细胞外寄生虫阴道毛滴虫引起的最常见的非病毒性性传播感染。这种感染是复发性的，没有持久的免疫力，通常没有症状，并与妊娠并发症和病毒感染的风险有关。这种寄生虫逃避免疫的分子机制还知之甚少。我们证明了Galectin-1和Galectin-3在人宫颈和阴道上皮细胞中表达，并作为优势表面原生动物脂磷脂多糖(LPG)的神经酰胺磷酸肌醇多聚糖核心(CPI-GC)的病原体识别受体。我们使用siRNA Galectin击倒上皮细胞克隆、重组Galectins、临床滴虫分离株和突变原生动物衍生物的体外模型来剖析Galectin-1和-3在滴虫感染背景下的功能。Galectin-1抑制促进吞噬细胞募集的趋化因子，从而消除细胞外原虫(IL-8)或桥接固有的获得性免疫(MIP-3α和RANTES(调节活化的正常T细胞表达和分泌))。沉默Galectin-1增加和加入外源Galectin-1抑制趋化因子对滴虫或CPI-GC/LPG的反应。相反，沉默Galectin-3降低了LPG对IL-8的反应。活的滴虫耗尽了细胞外的Galectin-3水平。临床分离株和与Galectin-3亲和力降低但对Galectin-1保持亲和力的突变滴虫CPI-GC抑制趋化因子的表达。因此，通过CPI-GC结合，毛滴虫能够调节半乳糖凝集素的生物利用度和功能，从而有利于其寄生生存。这些发现提示了控制滴虫病的新方法，并值得进一步研究临床分离株中半乳糖凝集素结合的多样性，作为寄生虫感染症状差异的可能来源。
Trichomoniasis is the most common non-viral sexually transmitted infection caused by the vaginotropic extracellular protozoan parasite Trichomonas vaginalis. The infection is recurrent, with no lasting immunity, often asymptomatic, and linked to pregnancy complications and risk of viral infection. The molecular mechanisms of immune evasion by the parasite are poorly understood. We demonstrate that galectin-1 and -3 are expressed by the human cervical and vaginal epithelial cells and act as pathogen-recognition receptors for the ceramide phosphoinositol glycan core (CPI-GC) of the dominant surface protozoan lipophosphoglycan (LPG). We used an in vitro model with siRNA galectin knockdown epithelial clones, recombinant galectins, clinical Trichomonas isolates, and mutant protozoan derivatives to dissect the function of galectin-1 and -3 in the context of Trichomonas infection. Galectin-1 suppressed chemokines that facilitate recruitment of phagocytes, which can eliminate extracellular protozoa (IL-8) or bridge innate to adaptive immunity (MIP-3α and RANTES (regulated on activation normal T cell expressed and secreted)). Silencing galectin-1 increased and adding exogenous galectin-1 suppressed chemokine responses to Trichomonas or CPI-GC/LPG. In contrast, silencing galectin-3 reduced IL-8 response to LPG. Live Trichomonas depleted the extracellular levels of galectin-3. Clinical isolates and mutant Trichomonas CPI-GC that had reduced affinity to galectin-3 but maintained affinity to galectin-1 suppressed chemokine expression. Thus via CPI-GC binding, Trichomonas is capable of regulating galectin bioavailability and function to the benefit of its parasitic survival. These findings suggest novel approaches to control trichomoniasis and warrant further studies of galectin-binding diversity among clinical isolates as a possible source for symptom disparity in parasitic infections.