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Research article2018Peer reviewedOpen access

Mast cell chymase decreases the severity of group B Streptococcus infections

Gendrin, Claire; Shubin, Nicholas J.; Boldenow, Erica; Merillat, Sean; Clauson, Morgan; Power, Danial; Doran, Kelly S.; Abrink, Magnus; Pejler, Gunnar; Rajagopal, Lakshmi; Piliponsky, Adrian M.

Abstract

Background: Group B Streptococcus (GBS) or Streptococcus agalactiae are beta-hemolytic gram-positive bacteria that colonize the lower genital tracts of women and are frequently associated with infections during pregnancy. Innate immune defenses are critical for controlling GBS dissemination and systemic infection. Mast cells are resident sentinel cells that come into contact with pathogens early during colonization and infection.Objective: We aimed to investigate the contribution of chymase to systemic GBS infection and rates of preterm birth.Methods: Pharmacologic and genetic approaches using mice deficient in mast cell protease (MCPT) 4, the mouse functional homologue of human chymase, were used.Results: Our studies show that mast cells release a protease with chymotrypsin-like cleavage specificity in response to GBS. Additionally, increased GBS systemic infection and preterm births were observed in MCPT4-deficient mice versus MCPT4-sufficient mice. Furthermore, we observed that proteolytic cleavage of the host extracellular matrix protein fibronectin by peritoneal cell-derived mast cell lysates diminished GBS adherence. Consistent with this observation, the increase in GBS dissemination and preterm births observed in MCPT4-deficient mice was abolished when GBS was deficient in expression of the fibronectin-binding protein SfbA.Conclusions: Taken together, our results suggest that the protective effect of MCPT4 against GBS dissemination and preterm labor can be attributed in part to MCPT4-mediated proteolysis of fibronectin. Our studies reveal a novel role of mast cells in defense against bacterial infections.

Keywords

Group B Streptococcus; mast cells; proteases; mouse mast cell protease 4; chymase; fibronectin

Published in

Journal of Allergy and Clinical Immunology
2018, Volume: 142, number: 1, pages: 120-129.e6
Publisher: MOSBY-ELSEVIER

      SLU Authors

      • Sustainable Development Goals

      Achieve gender equality and empower all women and girls

      UKÄ Subject classification

      Immunology

      Publication identifier

      DOI: https://doi.org/10.1016/j.jaci.2017.07.042

      Permanent link to this page (URI)

      https://res.slu.se/id/publ/96090