Institute of Physiology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
Berlin Institute of Health (BIH), 10178 Berlin, Germany.
Int J Mol Sci. 2021 Apr 8;22(8):3858. doi: 10.3390/ijms22083858.
Pneumonia due to respiratory infection with most prominently bacteria, but also viruses, fungi, or parasites is the leading cause of death worldwide among all infectious disease in both adults and infants. The introduction of modern antibiotic treatment regimens and vaccine strategies has helped to lower the burden of bacterial pneumonia, yet due to the unavailability or refusal of vaccines and antimicrobials in parts of the global population, the rise of multidrug resistant pathogens, and high fatality rates even in patients treated with appropriate antibiotics pneumonia remains a global threat. As such, a better understanding of pathogen virulence on the one, and the development of innovative vaccine strategies on the other hand are once again in dire need in the perennial fight of men against microbes. Recent data show that the secretome of bacteria consists not only of soluble mediators of virulence but also to a significant proportion of extracellular vesicles-lipid bilayer-delimited particles that form integral mediators of intercellular communication. Extracellular vesicles are released from cells of all kinds of organisms, including both Gram-negative and Gram-positive bacteria in which case they are commonly termed outer membrane vesicles (OMVs) and membrane vesicles (MVs), respectively. (O)MVs can trigger inflammatory responses to specific pathogens including and and as such, mediate bacterial virulence in pneumonia by challenging the host respiratory epithelium and cellular and humoral immunity. In parallel, however, (O)MVs have recently emerged as auspicious vaccine candidates due to their natural antigenicity and favorable biochemical properties. First studies highlight the efficacy of such vaccines in animal models exposed to (O)MVs from , and . An advanced and balanced recognition of both the detrimental effects of (O)MVs and their immunogenic potential could pave the way to novel treatment strategies in pneumonia and effective preventive approaches.
由细菌引起的呼吸道感染导致的肺炎，尤其是病毒、真菌或寄生虫引起的肺炎，是全世界所有传染病中导致成年人和婴儿死亡的主要原因。现代抗生素治疗方案和疫苗策略的引入有助于降低细菌性肺炎的负担，但由于部分全球人口无法获得或拒绝疫苗和抗生素，多重耐药病原体的出现，以及即使在接受适当抗生素治疗的患者中也存在高死亡率，肺炎仍然是一个全球性威胁。因此，一方面更好地了解病原体的毒力，另一方面开发创新的疫苗策略，再次成为人类对抗微生物的长期斗争中的迫切需要。最近的数据表明，细菌的分泌组不仅包含毒力的可溶性介质，而且还包含相当大比例的细胞外囊泡-脂质双层限定的颗粒，这些颗粒形成细胞间通讯的完整介质。细胞外囊泡是由各种生物体的细胞释放的，包括革兰氏阴性和革兰氏阳性细菌，在这种情况下，它们通常分别被称为外膜囊泡（OMV）和膜囊泡（MV）。（O）MV 可以引发针对特定病原体的炎症反应，包括 和 ，因此通过挑战宿主呼吸道上皮和细胞及体液免疫，介导肺炎中的细菌毒力。然而，平行的是，（O）MV 最近因其天然抗原性和良好的生化特性而成为有前途的疫苗候选物。初步研究强调了这些疫苗在暴露于 、 和 的 OMV 的动物模型中的功效。对（O）MV 的有害影响及其免疫原性的平衡认识，可以为肺炎的新型治疗策略和有效的预防方法铺平道路。
