Targeting complement hyperactivation: a novel therapeutic approach for severe pneumonia induced by influenza virus/staphylococcus aureus coinfection
Leili Jia, Haihua Luo, Lizhong Li, Mingyao Wang, Jiangfeng Liu, Yuan Liang, Shan Li, Yong Jiang, Juntao Yang, Hongbin Song
Abstract
Infections by the influenza virus are a significant and widespread global health threat, as these infections have an annual death toll ranging from 290,000 to 650,000. 1 A significant proportion of these fatalities are attributed to secondary bacterial pneumonia, a severe complication commonly caused by ubiquitous respiratory pathogens such as Staphylococcus aureus ( S. aureus ). 2 Of particular concern is the increased morbidity and mortality rates in individuals infected simultaneously with influenza virus and methicillin-resistant S. aureus (MRSA). 3 The concurrent presence of bacteria and influenza virus usually causes acute respiratory distress syndrome (ARDS), which is associated with acute lung injury (ALI), severe lung tissue edema, and widespread inflammation. Nevertheless, determining the complex mechanisms underlying the synergistic interplay will require further investigation with a suitable coinfection mouse model. In our previous study, we utilized different sequential coinfections at various time points to model influenza A virus and MRSA coinfection. We found that mice infected with influenza A virus (H1N1A/Puerto Rico/8/34, also known as PR8, at a concentration of 1 × 10 2 TCID50/ml) followed by exposure to MRSA (5 × 10 7 CFU/ml) after 2 days (referred to as the d-2 group, Supplementary Table S1 ) experienced significant mortality and lung tissue damage. Significantly, the d-2 group displayed the highest mortality rate and the most severe lung damage on the fifth day of coinfection. 4 Moreover, the increasing viral loads (Supplementary Fig. S1 ) hinted at a connection between lung damage and inflammatory cell infiltration, suggesting that the high mortality rate after H1N1A/MRSA coinfection may be due to overactivation of the inflammatory response, although validating this hypothesis will require further systematic investigation.