Splenic macrophages as the source of bacteraemia during pneumococcal pneumonia
| Autor: | Wen Yuan Chung, E. Richard Moxon, Ashley R. Dennison, Marcos I. Restrepo, Luisa Martinez-Pomares, Wei Shen Lim, Joseph J. Wanford, Carlos J. Orihuela, Ryan G Hames, M. R. Oggioni, Manish Pareek, David Carreno, Zydrune Jasiunaite, Kornelis Straatman, Peter W. Andrew |
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| Přispěvatelé: | Carreno D., Wanford J.J., Jasiunaite Z., Hames R.G., Chung W.Y., Dennison A.R., Straatman K., Martinez-Pomares L., Pareek M., Orihuela C.J., Restrepo M.I., Lim W.S., Andrew P.W., Moxon E.R., Oggioni M.R. |
| Rok vydání: | 2021 |
| Předmět: |
Medicine (General)
pathogenesi Macrophage Bacteremia Spleen human organ Azithromycin General Biochemistry Genetics and Molecular Biology sepsis Sepsis Pathogenesis Mice R5-920 medicine Animals Humans pneumonia Community-Acquired Infection therapy Lung Animal business.industry Macrophages pathogenesis General Medicine Pneumonia Pneumococcal bacterial infections and mycoses medicine.disease Bacterial Load respiratory tract diseases Community-Acquired Infections Disease Models Animal Pneumonia Streptococcus pneumoniae medicine.anatomical_structure Immunology Pneumococcal pneumonia Bacteraemia Medicine sepsi Female business Ex vivo Human Papio Research Paper medicine.drug |
| Zdroj: | EBioMedicine, Vol 72, Iss, Pp 103601-(2021) EBioMedicine |
| ISSN: | 2352-3964 |
| DOI: | 10.1016/j.ebiom.2021.103601 |
| Popis: | Background 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. Methods 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. Findings 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. Interpretation 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. Funding Oxford University, Wolfson Foundation, MRC, NIH, NIHR, and MRC and BBSRC studentships supported the work. |
| Databáze: | OpenAIRE |
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