CINDEFI (UNLP CONICET La Plata), School of Sciences, La Plata National University, La Plata, 1900, ArgentiLa Plata National Universityna.
Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald 17475, Germany.
Pathog Dis. 2022 Aug 24;80(1). doi: 10.1093/femspd/ftac031.
Gram-negative pathogenic bacteria constitutively shed outer membrane vesicles (OMVs) which play a significant role in the host-pathogen interaction, eventually determining the outcome of the infection. We previously found that Bordetella pertussis, the etiological agent of whooping cough, survives the innate interaction with human macrophages remaining alive inside these immune cells. Adenylate cyclase (CyaA), one of the main toxins of this pathogen, was found involved in the modulation of the macrophage defense response, eventually promoting bacterial survival within the cells. We here investigated whether B. pertussis OMVs, loaded with most of the bacterial toxins and CyaA among them, modulate the macrophage response to the bacterial infection. We observed that the pre-incubation of macrophages with OMVs led to a decreased macrophage defense response to the encounter with the bacteria, in a CyaA dependent way. Our results suggest that CyaA delivered by B. pertussis OMVs dampens macrophages protective function by decreasing phagocytosis and the bactericidal capability of these host cells. By increasing the chances of bacterial survival to the innate encounter with the macrophages, B. pertussis OMVs might play a relevant role in the course of infection, promoting bacterial persistence within the host and eventually, shaping the whole infection process.
革兰氏阴性病原菌持续释放外膜囊泡（OMVs），这些囊泡在宿主-病原体相互作用中起着重要作用，最终决定了感染的结果。我们之前发现，百日咳博德特氏菌是百日咳的病原体，它能够在与人类巨噬细胞的先天相互作用中存活下来，并在这些免疫细胞内继续存活。腺苷酸环化酶（CyaA）是该病原体的主要毒素之一，被发现参与调节巨噬细胞的防御反应，最终促进细菌在细胞内的存活。在这里，我们研究了百日咳博德特氏菌 OMVs（其中包含大多数细菌毒素和 CyaA）是否能够调节巨噬细胞对细菌感染的反应。我们观察到，巨噬细胞预先与 OMVs 孵育会导致巨噬细胞对与细菌相遇的防御反应减弱，这种减弱依赖于 CyaA。我们的结果表明，百日咳博德特氏菌 OMVs 中携带的 CyaA 通过降低吞噬作用和这些宿主细胞的杀菌能力来抑制巨噬细胞的保护功能。通过增加细菌在与巨噬细胞先天相遇时的存活机会，百日咳博德特氏菌 OMVs 可能在感染过程中发挥相关作用，促进细菌在宿主内的持续存在，并最终影响整个感染过程。
