Mast cell chymase decreases the severity of group B Streptococcus infections - 04/07/18
, Adrian M. Piliponsky, PhD a, b, ⁎ Abstract |
Background |
Group B Streptococcus (GBS) or Streptococcus agalactiae are β-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.
Le texte complet de cet article est disponible en PDF.Key words : Group B Streptococcus, mast cells, proteases, mouse mast cell protease 4, chymase, fibronectin
Abbreviations used : CFU, ECM, GBS, MCPT, MOI, PCMC, ROS, WT
Plan
| Supported by funding from the National Institutes of Health (NIH): grants R01AI100989, R21AI109222, and R01AI112619 (to L.R.); grant R01HL113351 to (A.M.P.), and Grant R01NS051247 (to K.S.D.). NIH training grant T32 HD007233 (Principal Investigator: Lisa Frenkel; supported E.B.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. |
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| Disclosure of potential conflict of interest: E. Boldenow has a National Institutes of Health (NIH)/National Institute of General Medical Sciences/National Research Service Reward training grant. K. S. Doran receives funds from an NIH institutional grant. L. Rajagopal's institution has 3 NIH grants on other work and has provided expert testimony on outside work. A. M. Piliponsky's institution has an NIH grant. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 142 - N° 1
P. 120 - juillet 2018 Retour au numéro
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