?eta 2-glycoprotein I protects mice against gram-negative septicaemia in a sexually dimorphic manner.

ABSTRACT: The immune responses of males and females to bacterial infections display differences. The mechanisms that underlie this sexual dimorphism are multifactorial. Lipopolysaccharide (LPS) contributes to the pathogenesis of endotoxaemia. We have previously demonstrated that the plasma protein beta-2 glycoprotein-1 (?2GPI) reduces LPS-induced inflammation in male mice. In the present study using a more robust infection model of septicaemia the role of ?2GPI is examined in both male and female wild type (WT) and ?2GPI deficient (?2GPI-/-) mice challenged with Escherichia coli (E. coli) intravenously. ?2GPI deficiency led to an increase of E. coli colony forming units (CFU) in the circulation of both male and female mice. In male ?2GPI-/- mice this was associated with a worse clinical severity score. This difference was not observed between female ?2GPI-/- and female WT mice. Male WT mice had decreased levels of total and increased levels of free thiol ?2GPI following administration of LPS or E. coli. This pattern of sexual dimorphic response was also observed in our cohort of humans with sepsis. These findings support a role for ?2GPI in modulating the sex-specific susceptibility to gram-negative septicaemia.

SUBMITTER: El-Assaad F 

PROVIDER: S-EPMC5557990 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature