Inflammatory monocytes enhance disease progression during post-influenza MRSA pneumonia

Abstract

Abstract Morbidity associated with influenza pandemics of the last century has been significantly associated with secondary bacterial infections. It is generally believed that the enhanced susceptibility to secondary bacterial infection is due to influenza-suppressed innate immunity. Interestingly, preceding influenza infection does not inhibit inflammatory cell recruitment during secondary bacterial infection. In fact, due to the recruitment of inflammatory monocytes, there are increased numbers of phagocytes in influenza and bacterial coinfected airways. The protective role of monocytes during influenza infection alone is well recognized; however, it is not clear how this phagocyte population contributes to post-influenza bacterial pneumonia. Using CC-Chemokine Receptor 2 deficient (CCR2−/−) mice defective in airway monocyte recruitment, we are currently investigating the role of inflammatory monocytes during influenza and methicillin-resistant Staphylococcus aureus (MRSA) coinfection. Specifically, C57BL/6 mice were infected intranasally with a sublethal dose of PR8 and subsequently MRSA on day seven post-influenza infection. Despite their delay in viral clearance, coinfected CCR2−/− mice exhibited significantly reduced bacterial burdens and importantly, improved survival rates compared with WT mice. Moreover, pro-inflammatory cytokine response in coinfected CCR2−/− mice was significantly decreased, suggesting an attenuation in lung inflammation. In summary, we found that by inhibiting bacterial clearance and perpetuating lung inflammation, inflammatory monocytes exacerbate adverse disease outcome during post-influenza MRSA pneumonia.