Mapping the local nasopharyngeal response to pneumococcal and PVM infection

Viral-bacterial interactions during co-infection are often synergistic including to increase disease severity. However, emerging evidence indicates that some bacteria can antagonise viral infection, although the host responses driving this process remains unclear. Using infant mice co-infected with Streptococcus pneumoniae and the Pneumonia Virus of Mice (a murine RSV analogue) to model antagonistic interactions, we found that prior bacterial colonisation enhances and prolongs anti-viral immune responses during co-infection, compared with viral infection alone. Transcriptomic, immunological, and histological analyses showed that pneumococcal colonisation enhanced and prolonged interferon signalling and NK/CD8+ T cell responses, accompanied by increased levels of anti-viral cytokines and chemokines during co-infection. Notably, over 50% of differentially expressed genes during co-infection were not differentially expressed in either infection alone, including numerous anti-viral genes. Our work shows that bacterial colonisation can modulate host immunity to impair viral infection and promote clearance, which has the potential to open novel therapeutic applications to combat viral infections.