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A7566 - Viral-Bacterial Discordance in Allergic Hosts
Author Block: A. E. Samarasinghe1, K. LeMessurier1, A. Iverson2, M. Palipane1, J. Rosch2; 1Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, United States, 2Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN, United States.
RATIONALE: Allergic asthma can be complicated by respiratory pathogens. Counterintuitively, asthmatics suffered less severe morbidity and mortality compared to non-asthmatics during the 2009 influenza A virus (IAV) pandemic. Using a novel mouse model of asthma and influenza comorbidity, we determined that IAV infection during allergic airways inflammation protects the host from influenza. Pathogen-pathogen interactions between IAV and Streptococcus pneumoniae (Spn) can lead to fatal outcomes in a healthy host. Interactions between IAV and Spn in an allergic host remain ambiguous. We hypothesized that allergic hosts will have less morbidity and mortality associated with Spn superinfection after influenza.
METHODS: Mice were subjected to the fungal asthma and influenza model by infecting mice rendered allergic with 1000 TCID50 of A/CA/04/2009 one week after the second allergen challenge. A week after the IAV infection, mice were infected with 600 CFU of Spn strain A66.1L. Physiologic, pathogen burden, and inflammatory responses were measured in addition to alterations to the resident pulmonary microbiome.
RESULTS: Infectious IAV was undetectable in the lungs at 72 h after Spn. Similar to animals infected with Spn alone, asthma+Spn mice cleared the bacteria completely by 72 h. Bacterial burden increased in the bronchoalveolar lavage fluid (BALF), lungs, and blood of mice in the IAV+Spn co-infection group. However, bacterial load in animals subjected to the fungal asthma model prior to viral and bacterial infections were significantly reduced in these niches with full clearance in some animals. More leukocytes were found in the BALF of mice infected with IAV. The number of macrophages was similar between all groups, while those in the asthma+IAV, asthma+Spn, asthma+IAV+Spn groups had prominent amounts of eosinophils and CD4+ T cells (30% each) in the airways, which was significantly higher than the asthma-only, IAV-only, Spn-only, and IAV+Spn groups. Neutrophils were most abundant in the IAV+Spn controls while the greatest number of CD8+ T cells was present in the IAV-only controls. The lung microbiome was significantly different in asthma+IAV+Spn. Remarkably, the asthma+IAV+Spn group did not have severe morbidity or mortality typically associated with IAV+Spn coinfection.
CONCLUSION: Based on these studies, we conclude that viral-bacterial synergy is altered by the allergic milieu and that the inflammatory profile in allergic airways may mitigate the impact of bacterial superinfection.