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

Abstract

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-deficient (FXIIIA-deficient) female mice exhibited significantly increased susceptibility to GBS infections. Additionally, female WT mice had increased levels of FXIIIA and were more resistant to GBS infection compared with 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 in which 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 effects of sexual dimorphism and mast cells on FXIIIA expression and its interactions with GBS adhesins that mediate bacterial dissemination and pathogenesis.

• Authors: Adrian M Piliponsky, Kavita Sharma, Phoenicia Quach, Alyssa Brokaw, Shayla Nguyen, Austyn Orvis, Siddhartha S Saha, Nyssa Becker Samanas, Ravin Seepersaud, Yu Ping Tang, Emily Mackey, Gauri Bhise, Claire Gendrin, Anna Furuta, Albert J Seo, Eric Guga, Irina Miralda, Michelle Coleman, Erin L Sweeney, Charlotte A Bäuml, Diana Imhof, Jessica M Snyder, Adam J Moeser, Lakshmi Rajagopal
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 132 Issue 20 (10 17 2022) ISSN: 1558-8238 [Electronic] United States
• PMID: 36006736 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)

Chemical References

• Androgens
• Fibronectins
• Fibrin
• Factor XIIIa
• Transglutaminases

Topics

• Androgens (metabolism)
• Animals
• Factor XIIIa (metabolism)
• Female
• Fibrin (metabolism)
• Fibronectins (genetics, metabolism)
• Humans
• Male
• Mast Cells (metabolism)
• Mice
• Streptococcal Infections (genetics)
• Streptococcus agalactiae (metabolism)
• Transglutaminases (metabolism)