Vasilevsky Sam, Stojanov Milos, Greub Gilbert, Baud David
a Materno-fetal and Obstetrics Research Unit ; Department of Obstetrics and Gynecology; Maternity; University Hospital ; Lausanne , Switzerland.
b Center for Research on Intracellular Bacteria; Institute of Microbiology; Faculty of Biology and Medicine; University of Lausanne and University Hospital ; Lausanne , Switzerland.
Virulence. 2016;7(1):11-22. doi: 10.1080/21505594.2015.1111509. Epub 2015 Nov 18.
Pmps (Polymorphic Membrane Proteins) are a group of membrane bound surface exposed chlamydial proteins that have been characterized as autotransporter adhesins and are important in the initial phase of chlamydial infection. These proteins all contain conserved GGA (I, L, V) and FxxN tetrapeptide motifs in the N-terminal portion of each protein. All chlamydial species express Pmps. Even in the chlamydia-related bacteria Waddlia chondrophila, a Pmp-like adhesin has been identified, demonstrating the importance of Pmps in Chlamydiales biology. Chlamydial species vary in the number of pmp genes and their differentially regulated expression during the infectious cycle or in response to stress. Studies have also demonstrated that Pmps are able to induce innate immune functional responses in infected cells, including production of IL-8, IL-6 and MCP-1, by activating the transcription factor NF-κB. Human serum studies have indicated that although anti-Pmp specific antibodies are produced in response to a chlamydial infection, the response is variable depending on the Pmp protein. In C. trachomatis, PmpB, PmpC, PmpD and PmpI were the proteins eliciting the strongest immune response among adolescents with and without pelvic inflammatory disease (PID). In contrast, PmpA and PmpE elicited the weakest antibody response. Interestingly, there seems to be a gender bias for Pmp recognition with a stronger anti-Pmp reactivity in male patients. Furthermore, anti-PmpA antibodies might contribute to adverse pregnancy outcomes, at least among women with PID. In vitro studies indicated that dendritic cells infected with C. muridarum were able to present PmpG and PmpF on their MHC class II receptors and T cells were able to recognize the MHC class-II bound peptides. In addition, vaccination with PmpEFGH and Major Outer Membrane Protein (MOMP) significantly protected mice against a genital tract C. muridarum infection, suggesting that Pmps may be an important component of a multi-subunit chlamydial vaccine. Thus, Pmps might be important not only for the pathogenesis of chlamydial infection, but also as potential candidate vaccine proteins.
多态性膜蛋白(Pmps)是一组膜结合的、表面暴露的衣原体蛋白,已被鉴定为自转运粘附素,在衣原体感染的初始阶段起重要作用。这些蛋白在每个蛋白的N端部分均含有保守的GGA(I、L、V)和FxxN四肽基序。所有衣原体物种均表达Pmps。甚至在与衣原体相关的细菌嗜软骨沃氏菌中,也已鉴定出一种类似Pmp的粘附素,这表明Pmps在衣原体生物学中具有重要意义。衣原体物种的pmp基因数量以及它们在感染周期中或对压力的反应中差异调节的表达各不相同。研究还表明,Pmps能够通过激活转录因子NF-κB在感染细胞中诱导先天性免疫功能反应,包括产生IL-8、IL-6和MCP-1。人体血清研究表明,尽管针对衣原体感染会产生抗Pmp特异性抗体,但该反应因Pmp蛋白而异。在沙眼衣原体中,PmpB、PmpC、PmpD和PmpI是在患有和未患有盆腔炎(PID)的青少年中引发最强免疫反应的蛋白。相比之下,PmpA和PmpE引发的抗体反应最弱。有趣的是,对于Pmp的识别似乎存在性别偏见,男性患者的抗Pmp反应更强。此外,抗PmpA抗体可能会导致不良妊娠结局,至少在患有PID的女性中如此。体外研究表明,感染鼠衣原体的树突状细胞能够在其MHC II类受体上呈递PmpG和PmpF,并且T细胞能够识别与MHC II类结合的肽。此外,用PmpEFGH和主要外膜蛋白(MOMP)进行疫苗接种可显著保护小鼠免受生殖道鼠衣原体感染,这表明Pmps可能是多亚基衣原体疫苗的重要组成部分。因此,Pmps可能不仅对衣原体感染的发病机制很重要,而且作为潜在的候选疫苗蛋白也很重要。