The role of IFN-γ/CXCL10 axis in Mycoplasma pneumonia infection

Background Mycoplasma pneumoniae caused lower respiratory tract infection, is highly prevalent in children and can be extremely dangerous for their health and well-being. However, the pathogenesis of this infection is complicated and thus has not been thoroughly studied. Methods ELISAs were used to analyze the expression levels of cytokines such as CXCL10 and IFN-γ in the peripheral blood and bronchoalveolar lavage fluid (BALF) of children with Mycoplasma pneumoniae pneumonia (MPP) and healthy controls. Western blot, RT-PCR, and flow cytometry were used to explore the effects of JAK-STAT1 signaling pathway on CXCL10 expressions. Results We discovered that, compared to control children, MPP patients expressed significantly higher levels of CXCL10 both in the peripheral blood and BALF, which was positively correlated with serum IFN-g and IgM levels as well as clinical presentations like days of hospitalization and fever duration. Moreover, numbers of macrophages, predominantly with a M1 phenotype, were significantly increased in BALFs of children of MPP. In vitro , coculture with IFN-γ or activated CD4 ⁺ Th1 cells significantly promoted CXCL10 expressions in THP-1 derived macrophages, which was largely reversed by siRNA-mediated down regulation of STAT1. In addition, IFN-g-stimulated macrophages greatly promoted the trans-migration of Th1 cells. Conclusions our data showed that Th1 cells-derived IFN-γ augments CXCL10 production in macrophages via the JAK-STAT1 pathway, which subsequently recruits more immune cells like Th1 cells into the infection sites, thereby constituting a positive feedback loop and aggravating the type I inflammatory responses in MPP patients.