Diurnal Differences in Intracellular Replication Within Splenic Macrophages Correlates With the Outcome of Pneumococcal Infection.
Diurnal Differences in Intracellular Replication Within Splenic Macrophages Correlates With the Outcome of Pneumococcal Infection.
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DOI：
10.3389/fimmu.2022.907461
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发表时间：
2022
影响因子：
7.3
通讯作者：
Oggioni, Marco R.
中科院分区：
文献类型：
--
作者：
Hames, Ryan G.;Jasiunaite, Zydrune;Ercoli, Giuseppe;Wanford, Joseph J.;Carreno, David;Straatman, Kornelis;Martinez-Pomares, Luisa;Yesilkaya, Hasan;Glenn, Sarah;Moxon, E. Richard;Andrew, Peter W.;Kyriacou, Charalambos P.;Oggioni, Marco R.
关键词：
昼夜节律影响细菌感染的进展和严重程度，包括由肺炎链球菌引起的细菌感染，但导致这种现象的机制在很大程度上仍然难以捉摸。随着我们对S.为了研究脾巨噬细胞内的肺炎球菌感染，我们试图研究脾内的事件是否与侵袭性肺炎球菌感染的不同结果相关。利用小鼠侵袭性肺炎球菌病（IPD）模型，在这里，我们报告说，在小鼠活动期（Zeitgeber时间15; 15小时后开始的光周期，3小时后开始的黑暗周期）感染导致败血症的发病明显快于休息期（Zeitgeber时间3; 3小时后开始的光周期）感染。这与活动期感染小鼠脾脏内肺炎球菌负荷在早期时间点显著高于静息期感染小鼠相关。这些脾脏的全切片共聚焦显微镜分析显示，肺炎球菌的数量显着更高，仅在边缘区嗜金属巨噬细胞（MMM）已知允许细胞内肺炎球菌复制作为败血症发作的先决条件。MMM内的肺炎球菌簇在活动期感染的小鼠中更丰富，并且随着时间的推移其大小增加，而在静止期感染的小鼠中，其大小减小并且存在于较低百分比的MMM中。在将肺炎球菌重新接种到血液中后，活动期感染小鼠中的菌血症水平以及血清IL-6和TNF-α浓度显著升高。这些数据通过将侵袭性肺炎球菌感染的易感性与MMM允许被吞噬细菌持续存在和复制的倾向的变化联系起来，极大地推进了我们对肺炎球菌感染的基础知识。这些发现还概述了一种罕见的情况，即生物体昼夜节律周期的活跃期在控制侵入性感染方面似乎起着适得其反的作用。
Circadian rhythms affect the progression and severity of bacterial infections including those caused by Streptococcus pneumoniae, but the mechanisms responsible for this phenomenon remain largely elusive. Following advances in our understanding of the role of replication of S. pneumoniae within splenic macrophages, we sought to investigate whether events within the spleen correlate with differential outcomes of invasive pneumococcal infection. Utilising murine invasive pneumococcal disease (IPD) models, here we report that infection during the murine active phase (zeitgeber time 15; 15h after start of light cycle, 3h after start of dark cycle) resulted in significantly faster onset of septicaemia compared to rest phase (zeitgeber time 3; 3h after start of light cycle) infection. This correlated with significantly higher pneumococcal burden within the spleen of active phase-infected mice at early time points compared to rest phase-infected mice. Whole-section confocal microscopy analysis of these spleens revealed that the number of pneumococci is significantly higher exclusively within marginal zone metallophilic macrophages (MMMs) known to allow intracellular pneumococcal replication as a prerequisite step to the onset of septicaemia. Pneumococcal clusters within MMMs were more abundant and increased in size over time in active phase-infected mice compared to those in rest phase-infected mice which decreased in size and were present in a lower percentage of MMMs. This phenomenon preceded significantly higher levels of bacteraemia alongside serum IL-6 and TNF-α concentrations in active phase-infected mice following re-seeding of pneumococci into the blood. These data greatly advance our fundamental knowledge of pneumococcal infection by linking susceptibility to invasive pneumococcal infection to variation in the propensity of MMMs to allow persistence and replication of phagocytosed bacteria. These findings also outline a somewhat rare scenario whereby the active phase of an organism’s circadian cycle plays a seemingly counterproductive role in the control of invasive infection.
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影响因子：
82.9
作者：
通讯作者：
--
DOI：
10.1084/jem.20161621
发表时间：
2017-05-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Deniset JF;Surewaard BG;Lee WY;Kubes P
通讯作者：
Kubes P
在新生儿败血症的早期诊断和管理中，血清IL-1Beta，IL-6，IL-8和TNF-Alpha水平。
影响因子：
4.6
作者：
Kurt, A Nese Citak;Aygun, A Denizmen;Godekmerdan, Ahmet;Kurt, Abdullah;Dogan, Yasar;Yilmaz, Erdal
通讯作者：
Yilmaz, Erdal
影响因子：
5.7
作者：
Magna, Melinda;Pisetsky, David S.
通讯作者：
Pisetsky, David S.
DOI：
10.1073/pnas.0307124101
发表时间：
2004-01-06
影响因子：
11.1
作者：
Kang, YS;Kim, JY;Park, CG
通讯作者：
Park, CG