Delayed viral clearance after respiratory tract infection results in prolonged inflammation in vitamin A deficient animals despite the presence of regulatory T cells (MUC1P.902)

Vitamin A deficiency (VAD) is a global health problem that persists in over half the countries in the world, affecting an estimated 250 million preschool children. VAD individuals suffer increased morbidity and mortality during enteric and respiratory infection, as vitamin A is an important regulator of immune system function. Previously, our lab has demonstrated that VAD mice have an impaired response to respiratory virus infection, exhibiting decreased IgA and CD8+ T cell responses to infection. Here we show that VAD mice fail to clear viral infection from the respiratory tract with the same efficiency as control vitamin A sufficient animals. We observed that prolonged viral presence can associate with an increased potential for T cell activation. As a result VAD animals experience a cytokine storm comprised of a mixed Th1/Th2 response including IFN-gamma, IL-4, IL-6 and IL-10 cytokines. Increased cytokine expression can be detected both on the transcriptional and protein level. Despite previous reports attributing VAD-related inflammation to a reduced frequency of regulatory T cells in the intestine, we observe no reduction in the number of FoxP3+ T cells in the respiratory tract of VAD animals compared to controls. Our results suggest that the increased inflammation observed during respiratory infection of VAD animals is due, at least in part, to poor IgA and CD8+ T cell responses and delayed viral clearance, and not exclusively to an absence of regulatory T cells.