Interferon-β Protects Hosts through Modulating the Inflammatory Responses of Macrophages in the Early Stage of Streptococcus pneumoniae Infection
CAO Sijia1, DOU Xiaoyun2, LU Chang1, MA Chenyu1, LIU Yusi3, LIAO Hongyi1, WANG Hong1*
This study aimed to investigate the effect of IFN-β (interferon-β) on host inflammatory responses in the early stage of S. pn (Streptococcus pneumoniae) infection. WT (wild type) mice and their PEMs (peritoneal exudate macrophages) were pretreated with exogenous rIFN-β (recombinant IFN-β), and culture medium-treated groups serve as controls. Meanwhile, endogenous IFNAR (interferon α/β receptor) deficient mice and PEMs were used, with WT counterparts as control groups. All the groups were exposed to strain D39, RT-PCR and ELISA were then used to measure the expression of IL-1β (interleukin-1β) and TNF-α (tumor necrosis factor-α). The pulmonary inflammatory infiltration and tissue injury were evaluated by HE-staining as well as dry/wet weight ratio in order to analyze the effect of IFN-β on host proinflammatory responses. To determine the bacterial clearance rate, phagocytosis analysis of RAW264.7 cells was carried out, and the bacterial load in lungs of infected mice was counted. Finally, the role of IFN-β on host resistance to S. pn was confirmed by survival rate analysis of mice. The results suggested that IFN-β inhibited the overexpression of IL-1β and TNF-α induced by D39. Compared with the NC (negative control) groups, rIFN-β pretreatment increased the phagocytosis of S. pn by RAW264.7 cells (P<0.001) and reduced the bacterial burden in lungs (P<0.01) and lung injury score of infected mice (P<0.05). Consistently, the bacterial load in lungs of IFNAR–/– mice was significantly higher than that of WT mice (P<0.001). Persistent higher level of local inflammation caused aggravated lung tissue damage of IFNAR–/– mice and enhanced mortality within nine days (P<0.05). However, there were no significant differences in body weight, lung dry/wet weight ratio or spleen index among the groups. Overall, IFN-β could maintain moderate local inflammatory responses by regulating the expression of proinflammatory cytokines in macrophages in the early stage of S. pn infection, which helped the host to clear bacteria, preventing local infection from developing into lethal infection.
CN
EN