Ozuna Hazel, Uriarte Silvia M, Demuth Donald R
Department of Microbiology and Immunology, School of Medicine, University of Louisville, Louisville, KY, United States.
Department of Oral Immunology and Infectious Diseases, School of Dentistry, University of Louisville, Louisville, KY, United States.
Front Immunol. 2021 Aug 12;12:707096. doi: 10.3389/fimmu.2021.707096. eCollection 2021.
is a gram-negative facultative anaerobe and an opportunistic oral pathogen, strongly associated with periodontitis and other inflammatory diseases. Periodontitis is a chronic inflammation of the periodontium resulting from the inflammatory response of the host towards the dysbiotic microbial community present at the gingival crevice. Previously, our group identified catecholamines and iron as the signals that activate the QseBC two-component system in , necessary for the organism to acquire iron as a nutrient to survive in the anaerobic environment. However, the source of catecholamines has not been identified. It has been reported that mouse neutrophils can release catecholamines. In periodontitis, large infiltration of neutrophils is found at the subgingival pocket; hence, we wanted to test the hypothesis that exploits human neutrophils as a source for catecholamines. In the present study, we showed that human neutrophils synthesize, store, and release epinephrine, one of the three main types of catecholamines. Human neutrophil challenge with induced exocytosis of neutrophil granule subtypes: secretory vesicles, specific granules, gelatinase granules, and azurophilic granules. In addition, by selectively inhibiting granule exocytosis, we present the first evidence that epinephrine is stored in azurophilic granules. Using QseC mutants, we showed that the periplasmic domain of the QseC sensor kinase is required for the interaction between and epinephrine. Finally, epinephrine-containing supernatants collected from human neutrophils promoted growth and induced the expression of the operon under anaerobic conditions. Based on our findings, we propose that promotes azurophilic granule exocytosis by neutrophils as an epinephrine source to promote bacterial survival.
是一种革兰氏阴性兼性厌氧菌和机会性口腔病原体，与牙周炎和其他炎症性疾病密切相关。牙周炎是牙周组织的慢性炎症，由宿主对牙龈沟中存在的生态失调微生物群落的炎症反应引起。此前，我们的研究小组确定儿茶酚胺和铁是激活 中QseBC双组分系统的信号，该系统是生物体获取铁作为营养物质以在厌氧环境中生存所必需的。然而，儿茶酚胺的来源尚未确定。据报道，小鼠中性粒细胞可以释放儿茶酚胺。在牙周炎中，龈下袋中发现大量中性粒细胞浸润；因此，我们想测试 利用人类中性粒细胞作为儿茶酚胺来源的假设。在本研究中，我们表明人类中性粒细胞合成、储存和释放肾上腺素，肾上腺素是三种主要儿茶酚胺类型之一。用 刺激人类中性粒细胞会诱导中性粒细胞颗粒亚型的胞吐作用：分泌囊泡、特异性颗粒、明胶酶颗粒和嗜天青颗粒。此外，通过选择性抑制颗粒胞吐作用，我们首次证明肾上腺素储存在嗜天青颗粒中。使用QseC突变体，我们表明QseC传感器激酶的周质结构域是 与肾上腺素相互作用所必需的。最后，从人类中性粒细胞收集的含肾上腺素的上清液在厌氧条件下促进了 生长并诱导了 操纵子的表达。基于我们的发现，我们提出 促进中性粒细胞将嗜天青颗粒作为肾上腺素来源进行胞吐作用，以促进细菌存活。
