Publikationsdatenbank

Caspase-6 mediates resistance against Burkholderia pseudomallei infection and influences the expression of detrimental cytokines (2017)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Bartel, Alexander (WE 16)

Göhler, André

Hopf, Verena

Breitbach, Katrin

Quelle

PLOS ONE

Bandzählung: 12

Heftzählung: 7

Seiten: e0180203

ISSN: 1932-6203

Sprache

Englisch

Verweise

URL (Volltext): https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0180203

DOI: 10.1371/journal.pone.0180203

Pubmed: 28686630

Kontakt

Institut für Veterinär-Epidemiologie und Biometrie

Königsweg 67
14163 Berlin
+49 30 838 56034
epi@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.