Mast cell degranulation impairs pneumococcus clearance in mice via IL-6 dependent and TNF-α independent mechanisms

Abstract

Background: Mast cells participate in immune responses by releasing potent immune system modifiers via degranulation. Due to currently reported controversial roles of mast cells in Streptococcus pneumoniae infections, this study aimed to determine the role and mechanism of mast cells in clearing S. pneumoniae in mice. Methods: In vivo mouse model of mast cell degranulation established by administration of C48/80 was evaluated for the influences of mast cell degranulation on bacterial colonization and inflammation. In vitro model was established to observe the influences of mast cell degranulation on phagocytic and bactericidal functions of neutrophils and macrophages. IL-6 null and TNF-α null mice on the C57BL/6 background were used to investigate the effects of inflammatory factors released by mast cell degranulation on bacterial clearance. Results: Mast cell degranulation increased IL-6 and TNF-α levels and immune cell numbers in nasal lavage fluid, and inhibited the bactericidal function of macrophages and neutrophils in vitro. It decreased the number of neutrophils and macrophages recruited to respiratory tract after S. pneumoniae challenge and inhibited the clearance of S. pneumoniae in mice. After pretreatment with C48/80, S. pneumoniae loads were significantly lower in IL-6 null mice than in wild type mice, while no differences were observed between TNF-α null and wild type mice. Conclusions: Mast cell degranulation can cause inflammation and impair immune cell recruitment to respiratory tract after S. pneumoniae challenge. Products of mast cell degranulation including IL-6 decreased the bactericidal function of neutrophils and macrophages. Through these mechanisms, mast cell degranulation inhibited clearance of S. pneumoniae in mice. Keywords: Degranulation, Inflammatory response, Mast cell, Streptococcus pneumoniae