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Extracellular Adenosine Protects against Lung Infection by Regulating Pulmonary Neutrophil Recruitment


Despite the presence of vaccines and antibiotic therapies, invasive Streptococcus pneumoniae (pneumococcus) infections, such as pneumonia, bacteremia and meningitis, remain a leading cause of mortality and morbidity worldwide. Understanding the host factors that influence the outcome of S. pneumoniae infection will allow us to design better therapies. Here, we elucidate the role of rapidly responding innate immune cells termed neutrophils, or PMNs (polymorphonuclear leukocytes), whose role in S. pneumoniae infection has long been controversial. We found that PMNs are initially required for controlling bacterial numbers, but their extended presence in the lungs leads to significant damage and poor control of infection. The signals that control the movement of PMNs into the infected lungs are not well understood. Here, we identified extracellular adenosine (EAD), a molecule produced by the host in response to cellular damage, as important in limiting PMN movement into the lungs upon pneumococcal challenge. Importantly, EAD-mediated control of PMNs was crucial for fighting lung infection by S. pneumoniae. This study may lead to the potential use of clinically available adenosine-based therapies to combat pneumococcal pneumonia in the future.


Vyšlo v časopise: Extracellular Adenosine Protects against Lung Infection by Regulating Pulmonary Neutrophil Recruitment. PLoS Pathog 11(8): e32767. doi:10.1371/journal.ppat.1005126
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005126

Souhrn

Despite the presence of vaccines and antibiotic therapies, invasive Streptococcus pneumoniae (pneumococcus) infections, such as pneumonia, bacteremia and meningitis, remain a leading cause of mortality and morbidity worldwide. Understanding the host factors that influence the outcome of S. pneumoniae infection will allow us to design better therapies. Here, we elucidate the role of rapidly responding innate immune cells termed neutrophils, or PMNs (polymorphonuclear leukocytes), whose role in S. pneumoniae infection has long been controversial. We found that PMNs are initially required for controlling bacterial numbers, but their extended presence in the lungs leads to significant damage and poor control of infection. The signals that control the movement of PMNs into the infected lungs are not well understood. Here, we identified extracellular adenosine (EAD), a molecule produced by the host in response to cellular damage, as important in limiting PMN movement into the lungs upon pneumococcal challenge. Importantly, EAD-mediated control of PMNs was crucial for fighting lung infection by S. pneumoniae. This study may lead to the potential use of clinically available adenosine-based therapies to combat pneumococcal pneumonia in the future.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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