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Border Patrol Gone Awry: Lung NKT Cell Activation by Exacerbates Tularemia-Like Disease


NKT cells are innate-like lymphocytes with a demonstrated role in a wide range of diseases. Often cited for their ability to rapidly produce a variety of cytokines upon activation, they have long been appreciated for their ability to “jump-start” the immune system and to shape the quality of both the innate and adaptive response. This understanding of their function has been deduced from in vitro experiments or through the in vivo administration of highly potent, chemically synthesized lipid ligands, which may not necessarily reflect a physiologically relevant response as observed in a natural infection. Using a mouse model of pulmonary tularemia, we report that intranasal infection with the live vaccine strain of F. tularensis rapidly activates NKT cells and promotes systemic inflammation, increased tissue damage, and a dysregulated immune response resulting in increased morbidity and mortality in infected mice. Our data highlight the detrimental effects of NKT cell activation and identify a potential new target for therapies against pulmonary tularemia.


Vyšlo v časopise: Border Patrol Gone Awry: Lung NKT Cell Activation by Exacerbates Tularemia-Like Disease. PLoS Pathog 11(6): e32767. doi:10.1371/journal.ppat.1004975
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004975

Souhrn

NKT cells are innate-like lymphocytes with a demonstrated role in a wide range of diseases. Often cited for their ability to rapidly produce a variety of cytokines upon activation, they have long been appreciated for their ability to “jump-start” the immune system and to shape the quality of both the innate and adaptive response. This understanding of their function has been deduced from in vitro experiments or through the in vivo administration of highly potent, chemically synthesized lipid ligands, which may not necessarily reflect a physiologically relevant response as observed in a natural infection. Using a mouse model of pulmonary tularemia, we report that intranasal infection with the live vaccine strain of F. tularensis rapidly activates NKT cells and promotes systemic inflammation, increased tissue damage, and a dysregulated immune response resulting in increased morbidity and mortality in infected mice. Our data highlight the detrimental effects of NKT cell activation and identify a potential new target for therapies against pulmonary tularemia.


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