Vitamin A-deficient mice experience increased viral antigens and enhanced cytokine/chemokine production in nasal tissues following respiratory virus infection despite the presence of FoxP3+ T cells. Mus musculus

Vitamin A deficiencies and insufficiencies affect hundreds of millions of people in both developing and developed countries. These individuals experience higher rates of mortality and increased morbidity during enteric and respiratory infections compared to those who are vitamin A sufficient. Previously, our laboratory has demonstrated that vitamin A-deficient (VAD) mice have significantly impaired virus-specific IgA and CD8+ T cell responses in the airways. Here we demonstrate that VAD mice experience enhanced cytokine/chemokine gene expression and release in the respiratory tract 10 days following virus infection compared to control vitamin A-sufficient animals. Cytokines/chemokines that are reproducibly upregulated at the gene expression and protein levels include IFNγ and IL-6. Despite previous indications that cytokine dysregulation in VAD animals might reflect low forkhead box (Fox)P3+ T cell frequencies, we found no reduction in FoxP3+ T cells in VAD respiratory tissues. As an alternative explanation for the high cytokine levels, we found that virus infection and viral antigen persistence were enhanced on day 10 post-infection in VAD animals compared to controls, and that respiratory tract tissues had an increased potential to activate virus-specific T cells. Results encourage cautious management of virus infections in patients with VAD; efforts to enhance FoxP3+ T cell frequencies and quell immune effectors might in some cases exacerbate disease if virus has not been cleared. Overall design: We used microarrays to explore the gene expression profiles differentially expressed in nasal-associated lymph tissue (NALT) lymphocytes from vitamin A-sufficient and vitamin A-deficient mice following infection with Sendai virus.