Hovingh Elise S, van den Broek Bryan, Jongerius Ilse
Department of Medical Microbiology, University Medical Center UtrechtUtrecht, Netherlands; Centre for Infectious Disease Control, National Institute for Public Health and the EnvironmentBilthoven, Netherlands.
Department of Medical Microbiology, University Medical Center Utrecht Utrecht, Netherlands.
Front Microbiol. 2016 Dec 20;7:2004. doi: 10.3389/fmicb.2016.02004. eCollection 2016.
The human complement system plays an important role in the defense against invading pathogens, inflammation and homeostasis. Invading microbes, such as bacteria, directly activate the complement system resulting in the formation of chemoattractants and in effective labeling of the bacteria for phagocytosis. In addition, formation of the membrane attack complex is responsible for direct killing of Gram-negative bacteria. In turn, bacteria have evolved several ways to evade complement activation on their surface in order to be able to colonize and invade the human host. One important mechanism of bacterial escape is attraction of complement regulatory proteins to the microbial surface. These molecules are present in the human body for tight regulation of the complement system to prevent damage to host self-surfaces. Therefore, recruitment of complement regulatory proteins to the bacterial surface results in decreased complement activation on the microbial surface which favors bacterial survival. This review will discuss recent advances in understanding the binding of complement regulatory proteins to the bacterial surface at the molecular level. This includes, new insights that have become available concerning specific conserved motives on complement regulatory proteins that are favorable for microbial binding. Finally, complement evasion molecules are of high importance for vaccine development due to their dominant role in bacterial survival, high immunogenicity and homology as well as their presence on the bacterial surface. Here, the use of complement evasion molecules for vaccine development will be discussed.
人类补体系统在抵御入侵病原体、炎症反应和内环境稳态中发挥着重要作用。入侵的微生物，如细菌，可直接激活补体系统，导致趋化因子的形成，并有效地标记细菌以便吞噬。此外，膜攻击复合物的形成负责直接杀死革兰氏阴性菌。反过来，细菌也进化出了几种方法来逃避其表面的补体激活，以便能够在人类宿主中定殖和入侵。细菌逃逸的一个重要机制是将补体调节蛋白吸引到微生物表面。这些分子存在于人体中，用于严格调节补体系统，以防止对宿主自身表面造成损伤。因此，补体调节蛋白被招募到细菌表面会导致微生物表面的补体激活减少，这有利于细菌存活。本综述将讨论在分子水平上理解补体调节蛋白与细菌表面结合方面的最新进展。这包括对补体调节蛋白上有利于微生物结合的特定保守基序的新认识。最后，补体逃避分子因其在细菌存活中的主导作用、高免疫原性和同源性以及在细菌表面的存在，对疫苗开发具有高度重要性。在此，将讨论补体逃避分子在疫苗开发中的应用。
