Open AccessCaspase-6 mediates resistance against Burkholderia pseudomallei infection and influences the expression of detrimental cytokines
Author(s) -
Alexander Bartel,
André Göhler,
Verena Hopf,
Katrin Breitbach
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0180203
Subject(s) - melioidosis , burkholderia pseudomallei , biology , microbiology and biotechnology , immune system , innate immune system , immunology , cytokine , caspase , caspase 1 , inflammation , apoptosis , programmed cell death , bacteria , inflammasome , biochemistry , genetics
Caspase-6 is a member of the executioner caspases and known to play a role in innate and adaptive immune processes. However, its role in infectious diseases has rarely been addressed yet. We here examined the impact of caspase-6 in an in vivo infection model using the Gram-negative rod Burkholderia pseudomallei , causing the infectious disease melioidosis that is endemic in tropical and subtropical areas around the world. Caspase-6 -/- and C57BL/6 wild type mice were challenged with B . pseudomallei for comparing mortality, bacterial burden and inflammatory cytokine expression. Bone-marrow derived macrophages were used to analyse the bactericidal activity in absence of caspase-6. Caspase-6 deficiency was associated with higher mortality and bacterial burden in vivo after B . pseudomallei infection. The bactericidal activity of caspase-6 -/- macrophages was impaired compared to wild type cells. Caspase-6 -/- mice showed higher expression of the IL-1β gene, known to be detrimental in murine melioidosis. Expression of the IL-10 gene was also increased in caspase-6 -/- mice as early as 6 hours after infection. Treatment with exogenous IL-10 rendered mice more susceptible against B . pseudomallei challenge. Thus, caspase-6 seems to play a crucial role for determining resistance against the causative agent of melioidosis. To our knowledge this is the first report showing that caspase-6 is crucial for mediating resistance in an in vivo infection model. Caspase-6 influences the expression of detrimental cytokines and therefore seems to be important for achieving a well-balanced immune response that contributes for an efficient elimination of the pathogen.