Effect of immunoglobulin G isotype on the infectivity of Chlamydia trachomatis in a mouse model of intravaginal infection.
Effect of immunoglobulin G isotype on the infectivity of Chlamydia trachomatis in a mouse model of intravaginal infection.
复制标题
免疫球蛋白 G 同种型对小鼠阴道内感染模型中沙眼衣原体感染性的影响。
DOI：
10.1128/iai.65.7.2693-2699.1997
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发表时间：
1997
影响因子：
3.1
通讯作者：
delaMaza,LM
中科院分区：
文献类型：
--
作者：
Peterson,EM;Cheng,X;Motin,VL;delaMaza,LM
已有的体外中和系统表明，抗沙眼衣原体主要外膜蛋白(MOMP)的单抗(MAb)可以中和或增强这种微生物的感染力，这取决于单抗的同种类型和所用的宿主细胞。针对MOMP可变区4(VD4)的单抗在宿主细胞没有可检测到的Fc-GammaRIII受体或添加补体以阻断单抗与受体的相互作用的系统中测试时，可中和沙眼衣原体的感染性。然而，如果Fc-GammaRIII受体可用，针对VD4的免疫球蛋白G2B(IgG2b)单抗能够增强该病原体的感染性。用识别MOMP VD4中TLNPTIA序列但同型不同的两株单抗，E4(IgG2b)和E21(IgG1)，在体内测试单抗的同种类型是否调节小鼠阴道感染的结局。第三种单抗CP33(IgG2b)识别沙眼衣原体脂多糖，但不能中和沙眼衣原体的感染性，也进行了测试。用这3株单抗对沙眼衣原体E血清型(Bour)的基本体(EBS)进行处理，并将其接种于经孕酮处理的C3H/HeJ小鼠的阴道内。随后，对小鼠进行了为期5周的阴道培养监测。用针对MOMP VD4的单抗处理的EBS接种组，感染小鼠的数量显著减少(P<0.05)。单抗E4组小鼠感染率为30%，单抗E21组为10%。相比之下，接种经单抗CP33处理的EBS组和未处理的对照EBS组的小鼠感染率分别为100%和79%。因此，在这种情况下，在体内引入涂有单抗的EBS，没有增强IgG2b单抗的感染；相反，结果与体外中和结果相似，其中使用的是缺乏Fc GammaRIII受体的细胞。在小鼠阴道接种沙眼衣原体前后，分别给予单抗和纯化的免疫球蛋白作为对照。尽管在感染时，血清中的单抗水平和阴道中可检测到的单抗水平相对较高，但在接受单抗E21的动物中，只有适度的保护作用，60%的小鼠受到感染，而接受单抗E4、单抗CP33和免疫球蛋白G的小鼠的感染率为90%。然而，到感染第二周时，与对照组相比，接受了两种IgG2b单抗E4和CP33的小鼠阴道中回收的衣原体数量显著增加(P<；0.05)。综上所述，在沙眼衣原体感染过程中的某些时间段，针对沙眼衣原体表面成分的IgG2b单抗的存在可能在增强该病原体的传染性方面发挥作用。
It has been previously shown with an in vitro neutralization system that monoclonal antibodies (MAbs) to the major outer membrane protein (MOMP) of Chlamydia trachomatis, depending on the isotype of the MAb and the host cell used, can either neutralize or enhance the infectivity of this organism. MAbs to variable domain 4 (VD 4) of MOMP have been described that neutralize the infectivity of C. trachomatis when tested in a system in which either the host cell does not have detectable Fc gammaRIII receptors or complement is added to block the interaction of the MAb with the receptor. However, if Fc gammaRIII receptors are available, immunoglobulin G2b (IgG2b) MAbs to the VD 4 are able to enhance the infectivity of this pathogen. Two MAbs that recognize the sequence TLNPTIA in VD 4 of the MOMP but differ in isotype, E4 (IgG2b) and E21 (IgG1), were used to test whether in vivo the isotype of the MAb modulates the outcome of a vaginal infection in a murine model. A third MAb, CP33 (IgG2b), that recognizes the chlamydial lipopolysaccharide but does not neutralize infectivity of C. trachomatis, was also tested. Elementary bodies (EBs) of C. trachomatis, serovar E (BOUR), were pretreated with the three MAbs and were used to inoculate the vaginas of C3H/HeJ mice which had been pretreated with progesterone. Subsequently mice were monitored over a 5-week period with vaginal cultures. In the groups that were inoculated with EBs pretreated with MAbs directed to VD 4 of MOMP, there was a significant decrease (P < 0.05) in the number of mice infected. Only 30% of the mice were infected in the MAb E4-treated group, and 10% were infected in the MAb E21 group. This was in contrast to the groups inoculated with EBs pretreated with MAb CP33 and control untreated EBs, which resulted in 100 and 79% of the mice infected, respectively. Therefore, in this setting in which EBs were introduced in vivo coated with MAb, there was no enhancement of infection by IgG2b MAbs; rather, the results paralled the in vitro neutralization results, in which cells lacking Fc gammaRIII receptors were employed. Mice were also given the MAbs, as well as purified IgG as a control, by intraperitoneal injection before and after intravaginal inoculation with C. trachomatis. Despite relatively high levels of MAbs in serum and detectable levels of MAbs in the vagina at the time of infection, there was only modest protection in animals receiving MAb E21, with 60% of the mice infected in contrast to 90% of the mice receiving MAb E4, MAb CP33, and IgG. However, by the second week of infection compared to controls, there was a significant increase (P < 0.05) in the amount of chlamydiae recovered from the vaginas of mice that had received the two IgG2b MAbs, E4 and CP33. In summary, the presence of IgG2b MAbs directed to surface components of C. trachomatis at certain times during the course of infection may play a role in enhancing the infectivity of this pathogen.