Mast Cell Chymase Decreases The Severity Of Group B Streptococcus Infections

Publication date: Available online 12 September 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Claire Gendrin, Nicholas J. Shubin, Erica Boldenow, Sean Merillat, Morgan Clauson, Danny Power, Kelly S. Doran, Magnus Abrink, Gunnar Pejler, Lakshmi Rajagopal, Adrian M. Piliponsky
BackgroundGroup B Streptococcus (GBS) or Streptococcus agalactiae are ß-hemolytic, Gram-positive bacteria that colonize the lower genital tract 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.ObjectiveWe aimed to investigate the contribution of chymase to systemic GBS infection and rates of preterm birth.MethodsPharmacological and genetic approaches using mice deficient in mast cell protease (MCPT)4, the mouse functional homolog of human chymase, were employed.ResultsOur studies show that, in response to GBS, mast cells release a protease with chymotrypsin-like cleavage specificity. Additionally, increased GBS systemic infection and preterm births were observed in MCPT4-deficient mice vs. MCPT4 sufficient mice. We further observed that proteolytic cleavage of the host extracellular matrix protein fibronectin by peritoneal cell-derived mast cell (PCMC) 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 were deficient in expression of the fibronectin binding protein, SfbA.ConclusionsTaken together, our results suggest that the protective effect of MCPT4 against GBS dissemination and preterm labor can in part be attributed to MCPT4-mediated proteolysis of fibronectin. Our studies reveal a novel role of mast cells in defense against bacterial infections.

Teaser

MCPT4-mediated downregulation of fibronectin via proteolytic cleavage contributes to reduced systemic GBS dissemination and preterm birth rates.


http://ift.tt/2h0So2r