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.

中文翻译：

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肥大细胞糜酶可降低B组链球菌感染的严重程度

背景

B组链球菌（GBS）或无乳链球菌是β-溶血性革兰氏阳性细菌，它们定植在女性的下生殖道中，并经常与怀孕期间的感染有关。先天性免疫防御对于控制GBS传播和全身感染至关重要。肥大细胞是常驻的前哨细胞，在定植和感染的早期就与病原体接触。

客观的

我们旨在调查糜酶对系统性GBS感染和早产率的贡献。

方法

使用了缺乏肥大细胞蛋白酶（MCPT）4的小鼠的药理学和遗传学方法，即人糜酶的小鼠功能同源物。

结果

我们的研究表明，肥大细胞对GBS的反应释放出一种具有胰凝乳蛋白酶样切割特异性的蛋白酶。此外，与MCPT4足够的小鼠相比，MCPT4缺乏的小鼠观察到GBS全身感染和早产增加。此外，我们观察到腹膜细胞衍生的肥大细胞裂解物对宿主细胞外基质蛋白纤连蛋白的蛋白水解切割减少了GBS的粘附。与该观察结果一致，当GBS缺乏纤连蛋白结合蛋白SfbA的表达时，就消除了MCPT4缺陷小鼠中GBS传播和早产的增加。

结论

两者合计，我们的结果表明，MCPT4对GBS传播和早产的保护作用可以部分归因于MCPT4介导的纤连蛋白的蛋白水解。我们的研究揭示了肥大细胞在防御细菌感染中的新型作用。