Sir William Dunn School of Pathology, University of Oxfordgrid.4991.5, Oxford, United Kingdom.
Infect Immun. 2022 Oct 20;90(10):e0037722. doi: 10.1128/iai.00377-22. Epub 2022 Oct 4.
Neisseria meningitidis and Neisseria gonorrhoeae are important human pathogens that have evolved to bind the major negative regulator of the complement system, complement factor H (CFH). However, little is known about the interaction of pathogens with CFH-related proteins (CFHRs) which are structurally similar to CFH but lack the main complement regulatory domains found in CFH. Insights into the role of CFHRs have been hampered by a lack of specific reagents. We generated a panel of CFHR-specific monoclonal antibodies and demonstrated that CFHR5 was bound by both pathogenic spp. We showed that CFHR5 bound to PorB expressed by both pathogens in the presence of sialylated lipopolysaccharide and enhanced complement activation on the surface of N. gonorrhoeae. Our study furthered our understanding of the interactions of CFHRs with bacterial pathogens and revealed that CFHR5 bound the meningococcus and gonococcus similar mechanisms.
脑膜炎奈瑟菌和淋病奈瑟菌是重要的人类病原体，它们已经进化到可以结合补体系统的主要负调节剂，即补体因子 H（CFH）。然而，对于结构上与 CFH 相似但缺乏 CFH 中主要补体调节结构域的 CFH 相关蛋白（CFHRs）与病原体的相互作用，我们知之甚少。由于缺乏特异性试剂，对 CFHRs 作用的研究受到了阻碍。我们生成了一组 CFHR 特异性单克隆抗体，并证明了这两种病原体都能结合 CFHR5。我们表明，CFHR5 在唾液酸化脂多糖存在的情况下与两种病原体表达的 PorB 结合，并增强淋病奈瑟菌表面的补体激活。我们的研究进一步加深了我们对 CFHRs 与细菌病原体相互作用的理解，并揭示了 CFHR5 以相似的机制结合脑膜炎球菌和淋球菌。
