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TNFα and IFNγ but Not Perforin Are Critical for CD8 T Cell-Mediated Protection against Pulmonary Infection


Bacterial pneumonia is one of the most common causes of death worldwide. Pulmonary infection of bacterium Yersinia pestis, the causative agent of plague, results in pneumonic plague and is extremely lethal. Mouse models of pulmonary Y. pestis infection are considered translational tools for the development of pneumonic plague countermeasures and studies of the basic mechanisms of immune defense against acutely lethal pulmonary bacterial infections. Here, we used several methods to investigate the functions that CD8 T cells exert to confer protection against pulmonary Y. pestis infection and evaluated their relative contributions. We found that although CD8 T cells have the ability to kill Y. pestis-infected cells, a function called cytotoxicity, this function is not required for CD8 T cells to protect against Y. pestis infection. In contrast, protection depends upon the ability of CD8 T cells to produce the cytokines TNFα and IFNγ, and mice whose T cells cannot produce these two cytokines are not protected. Therefore, we conclude that cytokine production, not cytotoxicity, is essential for CD8 T cell-mediated control of pulmonary Y. pestis infection and we suggest that assays detecting cytokine production may be useful correlates of vaccine efficacy against plague and other acutely lethal septic bacterial pneumonias.


Vyšlo v časopise: TNFα and IFNγ but Not Perforin Are Critical for CD8 T Cell-Mediated Protection against Pulmonary Infection. PLoS Pathog 10(5): e32767. doi:10.1371/journal.ppat.1004142
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004142

Souhrn

Bacterial pneumonia is one of the most common causes of death worldwide. Pulmonary infection of bacterium Yersinia pestis, the causative agent of plague, results in pneumonic plague and is extremely lethal. Mouse models of pulmonary Y. pestis infection are considered translational tools for the development of pneumonic plague countermeasures and studies of the basic mechanisms of immune defense against acutely lethal pulmonary bacterial infections. Here, we used several methods to investigate the functions that CD8 T cells exert to confer protection against pulmonary Y. pestis infection and evaluated their relative contributions. We found that although CD8 T cells have the ability to kill Y. pestis-infected cells, a function called cytotoxicity, this function is not required for CD8 T cells to protect against Y. pestis infection. In contrast, protection depends upon the ability of CD8 T cells to produce the cytokines TNFα and IFNγ, and mice whose T cells cannot produce these two cytokines are not protected. Therefore, we conclude that cytokine production, not cytotoxicity, is essential for CD8 T cell-mediated control of pulmonary Y. pestis infection and we suggest that assays detecting cytokine production may be useful correlates of vaccine efficacy against plague and other acutely lethal septic bacterial pneumonias.


Zdroje

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Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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PLOS Pathogens


2014 Číslo 5
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