Allergic inflammation alters the lung microbiome and hinders synergistic co-infection with H1N1 influenza virus and Streptococcus pneumoniae in C57BL/6 mice

Asthma is a chronic airways condition that can be exacerbated during respiratory infections. Our previous work, together with epidemiologic findings that asthmatics were less likely to suffer from severe influenza during the 2009 pandemic, suggest that additional complications of influenza such as increased susceptibility to bacterial superinfection, may be mitigated in allergic hosts. To test this hypothesis, we developed a murine model of ‘triple-disease’ in which mice rendered allergic to Aspergillus fumigatus were co-infected with influenza A virus and Streptococcus pneumoniae seven days apart. Significant alterations to known synergistic effects of co-infection were noted in the allergic mice including reduced morbidity and mortality, bacterial burden, maintenance of alveolar macrophages, and reduced lung inflammation and damage. The lung microbiome of allergic mice differed from that of non-allergic mice during co-infection and antibiotic-induced perturbation to the microbiome rendered allergic animals susceptible to severe morbidity. Our data suggest that responses to co-infection in allergic hosts likely depends on the immune and microbiome states and that antibiotics should be used with caution in individuals with underlying chronic lung disease.