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百日咳博德特氏菌外膜囊泡可损害中性粒细胞的杀菌活性。

Bordetella pertussis outer membrane vesicles impair neutrophil bactericidal activity.

机构信息

CINDEFI (UNLP CONICET La Plata), School of Sciences, La Plata National University, La Plata, Argentina.

CINDEFI (UNLP CONICET La Plata), School of Sciences, La Plata National University, La Plata, Argentina.

出版信息

Microbes Infect. 2024 Nov-Dec;26(8):105375. doi: 10.1016/j.micinf.2024.105375. Epub 2024 Jun 6.

Abstract

Neutrophils constitute the primary defense against bacterial infections, yet certain pathogens express virulence factors that enable them to subvert neutrophils-mediated killing. Outer membrane vesicles (OMVs) have emerged as a secretory system through which bacteria deliver virulence factors to host cells. OMVs from Bordetella pertussis, the etiological agent of whooping cough, are loaded with most of bacterial virulence factors, including CyaA, which plays a key role in B. pertussis evasion of neutrophils bactericidal activity. In our study, we investigated the role of B. pertussis OMVs in bacterial interaction with neutrophils. We observed that interaction of OMVs with neutrophils led to a decrease in the expression of cell surface CR3 and FcγRs, an effect dependent on the CyaA toxin delivered by these vesicles. This decreased receptor expression led to reduced bacterial uptake by neutrophils, irrespective of the presence of opsonic antibodies. Moreover, CyaA delivered by OMVs hindered intracellular bactericidal trafficking, promoting bacterial intracellular survival. When both bacteria and OMVs were opsonized, competition between opsonized OMVs and B. pertussis for FcγRs on neutrophils led to a significant decrease in bacterial uptake. Overall, our findings suggest that B. pertussis OMVs promote bacterial survival to the encounter with neutrophils in both naïve and immunized individuals.

摘要

中性粒细胞是抵御细菌感染的主要防线,但某些病原体表达的毒力因子使它们能够颠覆中性粒细胞介导的杀伤作用。外膜囊泡(OMVs)作为一种分泌系统出现,细菌通过该系统将毒力因子输送到宿主细胞。百日咳博德特氏菌(百日咳的病原体)的 OMVs 装载了大多数细菌毒力因子,包括 CyaA,它在百日咳博德特氏菌逃避中性粒细胞杀菌活性中起着关键作用。在我们的研究中,我们研究了百日咳博德特氏菌 OMVs 在细菌与中性粒细胞相互作用中的作用。我们观察到,OMVs 与中性粒细胞的相互作用导致细胞表面 CR3 和 FcγRs 的表达减少,这一效应依赖于这些囊泡中携带的 CyaA 毒素。这种受体表达的减少导致中性粒细胞摄取细菌减少,而与调理抗体的存在与否无关。此外,OMVs 中携带的 CyaA 阻碍了细胞内杀菌运输,促进了细菌的细胞内存活。当细菌和 OMVs 都被调理时,调理后的 OMVs 和百日咳博德特氏菌与中性粒细胞上的 FcγRs 竞争,导致细菌摄取量显著减少。总的来说,我们的研究结果表明,百日咳博德特氏菌 OMVs 促进了细菌的存活,使其能够在未免疫和免疫个体中遇到中性粒细胞。

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