Neutrophil Elastase Causes Tissue Damage That Decreases Host Tolerance to Lung Infection with Species


Two distinct defense strategies can protect the host from infection:
resistance is the ability to destroy the infectious agent, and tolerance is the ability to withstand infection by minimizing the negative impact it has on the host's health without directly affecting pathogen burden. Burkholderia pseudomallei, the causative agent of melioidosis, is a Gram-negative intracellular bacteria that is categorized as a potential bioterrorism agent. Using murine models, we previously demonstrated that during B. pseudomallei infection, production of IL-1β is deleterious as it recruited excessive neutrophils to the site of infection. In the present work, we focused on the detrimental role of neutrophils during infection with B. pseudomallei and B. thailandensis. Here, we demonstrate that the excessive recruitment of neutrophils to the site of infection causes tissue damage because of release of the protease elastase. Mice lacking neutrophil elastase have increased survival even though they carry an equal amount of bacteria in their organs as compared to the wild-type C57BL/6J. Thus, neutrophil elastase is a host defense mechanism that causes tissue damage and reduces host tolerance to infection.


Vyšlo v časopise: Neutrophil Elastase Causes Tissue Damage That Decreases Host Tolerance to Lung Infection with Species. PLoS Pathog 10(8): e32767. doi:10.1371/journal.ppat.1004327
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.ppat.1004327

Souhrn

Two distinct defense strategies can protect the host from infection:
resistance is the ability to destroy the infectious agent, and tolerance is the ability to withstand infection by minimizing the negative impact it has on the host's health without directly affecting pathogen burden. Burkholderia pseudomallei, the causative agent of melioidosis, is a Gram-negative intracellular bacteria that is categorized as a potential bioterrorism agent. Using murine models, we previously demonstrated that during B. pseudomallei infection, production of IL-1β is deleterious as it recruited excessive neutrophils to the site of infection. In the present work, we focused on the detrimental role of neutrophils during infection with B. pseudomallei and B. thailandensis. Here, we demonstrate that the excessive recruitment of neutrophils to the site of infection causes tissue damage because of release of the protease elastase. Mice lacking neutrophil elastase have increased survival even though they carry an equal amount of bacteria in their organs as compared to the wild-type C57BL/6J. Thus, neutrophil elastase is a host defense mechanism that causes tissue damage and reduces host tolerance to infection.


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Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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