Mast cell derived factor XIIIA contributes to sexual dimorphic defense against group B Streptococcal infections.

Invasive bacterial infections remain a major cause of human morbidity. Group B Streptococcus (GBS) are Gram-positive bacteria that cause invasive infections in humans. Here, we show that Factor XIIIA (FXIIIA) -deficient female mice exhibited significantly increased susceptibility to GBS infections. Additionally, female wild-type mice had increased levels of FXIIIA and were more resistant to GBS infection compared to isogenic male mice. We observed that administration of exogenous FXIIIA to male mice increased host resistance to GBS infection. Conversely, administration of a FXIIIA transglutaminase inhibitor to female mice decreased host resistance to GBS infection. Interestingly, male gonadectomized mice exhibited decreased sensitivity to GBS infection, suggesting a role for gonadal androgens in host susceptibility. FXIIIA promoted GBS entrapment within fibrin clots by crosslinking fibronectin with ScpB, a fibronectin binding GBS surface protein. Thus, ScpB-deficient GBS exhibited decreased entrapment within fibrin clots in vitro and increased dissemination during systemic infections. Finally, using mice where FXIIIA expression was depleted in mast cells, we observed that mast cell derived FXIIIA contributes to host defense against GBS infection. Our studies provide insights into the effect of sexual dimorphism and mast cells on FXIIIA expression and its interactions with GBS adhesins that mediate bacterial dissemination and pathogenesis.