Vitamin A deficiency dysregulates immune responses toward influenza virus and increases mortality after bacterial coinfections.

Background Secondary bacterial coinfections are ranked as a leading cause of hospitalization and morbidity associated with influenza. Because vitamin A deficiencies (VAD) and insufficiencies are frequent in both developed and developing countries, we asked how VAD influences coinfection severity. Methods VAD and control mice were infected with influenza virus for evaluation of inflammatory cytokines, cellular immune responses, and viral clearance. Influenza-infected mice were coinfected with Streptococcus pneumoniae to study weight loss and survival. Results Naive VAD mouse lungs exhibited dysregulated immune function. Neutrophils were enhanced in frequency and there was a significant reduction in RANTES, a chemokine instrumental in T cell homing and recruitment. After influenza virus infection, VAD mice experienced failures in CD4+ T cell recruitment and B cell organization into lymphoid structures in the lung. VAD mice exhibited higher viral titers than controls and slow viral clearance. There were elevated levels of inflammatory cytokines and innate cell subsets in the lungs. However, arginase, a marker of alternatively activated M2 macrophages, was rare. When influenza infected VAD animals were exposed to bacteria, they suffered 100% mortality. Conclusion Data showed that VAD dysregulated the immune response. Consequently, secondary bacterial infections were 100% lethal in influenza infected VAD mice.