The Hunger Games: Aggregatibacter actinomycetemcomitans Exploits Human Neutrophils As an Epinephrine Source for Survival.
The Hunger Games: Aggregatibacter actinomycetemcomitans Exploits Human Neutrophils As an Epinephrine Source for Survival.
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DOI：
10.3389/fimmu.2021.707096
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发表时间：
2021
影响因子：
7.3
通讯作者：
Demuth DR
中科院分区：
文献类型：
--
作者：
Ozuna H;Uriarte SM;Demuth DR
伴放线聚集杆菌是一种革兰氏阴性兼性厌氧菌，是一种口腔条件致病菌，与牙周炎等炎症性疾病密切相关。牙周炎是由宿主对存在于龈沟处的微生物群落的炎症反应引起的牙周组织的慢性炎症。在此之前，我们的小组确定了儿茶酚胺和铁作为激活A.放线菌共生体，是生物体获得铁作为营养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，在龈下袋中发现大量的中性粒细胞浸润，因此，我们想检验A。伴放线菌利用人嗜中性粒细胞作为儿茶酚胺的来源。在目前的研究中，我们发现，人类中性粒细胞合成，储存和释放肾上腺素，三种主要类型的儿茶酚胺之一。用A.伴放线菌引起中性粒细胞颗粒亚型的胞吐：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，我们提出的第一个证据表明，肾上腺素储存在嗜天青颗粒。使用QseC突变体，我们发现QseC传感器激酶的周质结构域是A.放线菌共生菌和肾上腺素。最后，从人中性粒细胞收集的含肾上腺素的上清液促进A。在厌氧条件下，放线菌共生菌生长并诱导qseBC操纵子的表达。根据我们的研究结果，我们建议A.伴随放线菌促进嗜中性粒细胞的嗜天青颗粒胞吐作用，作为肾上腺素来源以促进细菌存活。
Aggregatibacter actinomycetemcomitans 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 A. actinomycetemcomitans, 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 A. actinomycetemcomitans 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 A. actinomycetemcomitans 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 A. actinomycetemcomitans and epinephrine. Finally, epinephrine-containing supernatants collected from human neutrophils promoted A. actinomycetemcomitans growth and induced the expression of the qseBC operon under anaerobic conditions. Based on our findings, we propose that A. actinomycetemcomitans promotes azurophilic granule exocytosis by neutrophils as an epinephrine source to promote bacterial survival.
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影响因子：
32.4
作者：
Campbell EL;Bruyninckx WJ;Kelly CJ;Glover LE;McNamee EN;Bowers BE;Bayless AJ;Scully M;Saeedi BJ;Golden-Mason L;Ehrentraut SF;Curtis VF;Burgess A;Garvey JF;Sorensen A;Nemenoff R;Jedlicka P;Taylor CT;Kominsky DJ;Colgan SP
通讯作者：
Colgan SP
影响因子：
3.6
作者：
Chatterjee A;O'Brian MR
通讯作者：
O'Brian MR
影响因子：
3.4
作者：
Edmisson JS;Tian S;Armstrong CL;Vashishta A;Klaes CK;Miralda I;Jimenez-Flores E;Le J;Wang Q;Lamont RJ;Uriarte SM
通讯作者：
Uriarte SM
影响因子：
3.2
作者：
Armstrong, Cortney L.;Klaes, Christopher K.;Uriarte, Silvia M.
通讯作者：
Uriarte, Silvia M.
影响因子：
3.8
作者：
Gholizadeh, Pourya;Pormohammad, Ali;Kafil, Hossein Samadi
通讯作者：
Kafil, Hossein Samadi