Activity of NLRP3 inflammasome in MRSA pneumonia secondary to influenza A virus infection in mice

AIM To evaluate the activity of NLRP3 inflammasome in methicillin-resistant Staphylococcus aureus （MRSA） pneumonia secondary to influenza A virus （IAV） HIN1 in mice. METHODS Pneumonia model caused by intranasal inoculation with only MRSA for 24 h （MRSA group） and with MRSA for 24 h secondary to IAV H1N1 infection for 6 d in advance （H1N1+MRSA group）in C57BL/6 mice were established.The mRNA expression of NLRP3， caspase-1 and interleukin-1β （IL-1β） in lung tissues was detected by RT-qPCR. The protein levels of NLRP3 and caspase-1 in the lung tissues were determined by Western blot. The serum concentration of IL-1β was measured by ELISA. The pathological changes of the lung tissues were examined. The correlation between rate of weight loss during infection and serum concentration of IL-1β was investigated. RESULTS In MRSA group， the mRNA levels and relative protein expression levels of NLRP3 and caspase-1 showed no difference compared with control group （P>0.05）， while the mRNA expression of IL-1β and the serum concentration of IL-1β were significantly higher than those in control group （P<0.01）. In H1N1+MRSA group， the mRNA levels and relative protein expression levels of NLRP3 and caspase-1 were significantly higher than those in control group， as well as higher than those in MRSA group （P<0.01）， the mRNA level and serum concentration of IL-1β were significantly higher than those in control group but lower than those in MRSA group （P<0.01）. The pathological observation of the lung in MRSA group showed inflammatory responses， and severer pneumonia in H1N1+MRSA group was found. The rate of weight loss in the mice of MRSA group and H1N1+MRSA group was negatively correlated with the serum concentration of IL-1β. CONCLUSION IL-1β expression induced by MRSA infection is in a NLRP3 inflammasome independent manner. It also suggests that IAV H1N1 infection in advance down regulates the expression of IL-1β in secondary infection with MRSA， which may contribute to the mechanism of MRSA pneumonia secondary to IAV infection.