Splenic macrophages as the source of bacteraemia during pneumococcal pneumonia.
Splenic macrophages as the source of bacteraemia during pneumococcal pneumonia.
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DOI：
10.1016/j.ebiom.2021.103601
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发表时间：
2021-10
期刊：
影响因子：
11.1
通讯作者：
Oggioni MR
中科院分区：
文献类型：
--
作者：
Carreno D;Wanford JJ;Jasiunaite Z;Hames RG;Chung WY;Dennison AR;Straatman K;Martinez-Pomares L;Pareek M;Orihuela CJ;Restrepo MI;Lim WS;Andrew PW;Moxon ER;Oggioni MR
严重的社区获得性肺炎球菌肺炎通常与菌血症有关。虽然假设菌血症仅源于从肺部进入血液的肺炎球菌，但尚不清楚其他器官在菌血症的发病机制中是否重要。使用三种模型，我们测试了脾脏在肺炎相关菌血症中的相关性。我们使用体外灌注的人类脾脏来探索细菌复制的许可性，一个非人灵长类动物模型来检查肺炎期间脾脏受累，一个小鼠肺炎-菌血症模型来证明脾脏受累与侵袭性疾病相关。在这里，我们提出的证据表明，脾脏是肺炎期间菌血症的储存库。我们发现，在感染肺炎球菌的人脾脏中，巨噬细胞内可检测到数量增加的细菌簇。在非人类灵长类动物中也发现了这些群集。当用非治疗剂量的阿奇霉素（阿奇霉素对肺炎没有作用，但集中在脾巨噬细胞内）治疗鼻内感染小鼠时，脾脏和血液中没有细菌，重要的是小鼠没有疾病迹象。我们得出结论，细菌负荷在脾脏，而不是肺，与菌血症的发生有关。这支持了一种假设，即在肺炎球菌肺炎相关的全身感染中，脾脏而不是肺部是细菌的主要来源；这一发现为使用包括大环内酯类药物在内的联合疗法治疗严重社区获得性肺炎球菌肺炎提供了机制基础。牛津大学，沃尔夫森基金会，MRC， NIH， NIHR， MRC和BBSRC学生支持这项工作。
Severe community-acquired pneumococcal pneumonia is commonly associated with bacteraemia. Although it is assumed that the bacteraemia solely derives from pneumococci entering the blood from the lungs it is unknown if other organs are important in the pathogenesis of bacteraemia. Using three models, we tested the relevance of the spleen in pneumonia-associated bacteraemia. We used human spleens perfused ex vivo to explore permissiveness to bacterial replication, a non-human primate model to check for splenic involvement during pneumonia and a mouse pneumonia-bacteraemia model to demonstrate that splenic involvement correlates with invasive disease. Here we present evidence that the spleen is the reservoir of bacteraemia during pneumonia. We found that in the human spleen infected with pneumococci, clusters with increasing number of bacteria were detectable within macrophages. These clusters also were detected in non-human primates. When intranasally infected mice were treated with a non-therapeutic dose of azithromycin, which had no effect on pneumonia but concentrated inside splenic macrophages, bacteria were absent from the spleen and blood and importantly mice had no signs of disease. We conclude that the bacterial load in the spleen, and not lung, correlates with the occurrence of bacteraemia. This supports the hypothesis that the spleen, and not the lungs, is the major source of bacteria during systemic infection associated with pneumococcal pneumonia; a finding that provides a mechanistic basis for using combination therapies including macrolides in the treatment of severe community-acquired pneumococcal pneumonia. Oxford University, Wolfson Foundation, MRC, NIH, NIHR, and MRC and BBSRC studentships supported the work.
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影响因子：
10
作者：
Lim, W. S.;Smith, D. L.;Welham, S. A.
通讯作者：
Welham, S. A.
影响因子：
4.3
作者：
Arnold, Forest W.;Lopardo, Gustavo;Feldman, Charles
通讯作者：
Feldman, Charles
影响因子：
28.2
作者：
De la Calle, C.;Ternavasio-de la Vega, H. G.;Soriano, A.
通讯作者：
Soriano, A.
研究肺炎球菌类型的诱导物质转化的化学性质：通过从III型肺炎球菌分离出的脱氧核糖核酸分数诱导转化。
DOI：
10.1084/jem.79.2.137
发表时间：
1944-02-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Avery OT;Macleod CM;McCarty M
通讯作者：
McCarty M
影响因子：
56.3
作者：
Cohen, Jonathan;Vincent, Jean-Louis;Pelfrene, Eric
通讯作者：
Pelfrene, Eric