Vitamin A deficient mice exhibit impaired viral clearance, increased inflammation and altered immune response during respiratory viral infection

Abstract

Abstract Vitamin A deficiency (VAD) is prevalent in developing countries and is associated with increased mortality after respiratory viral infections. Vitamin A can only be acquired through the diet, and millions of pregnant women and young children are deficient; however, the effects of VAD on the immune response are not completely understood. Pregnant C57BL/6 mice were placed on a VAD diet at gestational day five, pups remained on this diet after birth. At 8 weeks of age, control and VAD mice were infected intranasally with a sub-lethal dose of Sendai Virus (SeV), a natural mouse pathogen. Body weight loss in control mice peaked at day 7 post-infection, while VAD mice continued to lose weight until day 11 post-infection. This was associated with delayed clearance of virus, elevated cytokines TNFα, IL-4, and IL-17, and increased numbers of inflammatory cells in the VAD lungs. Flow cytometry showed significantly increased percentages of neutrophils on days 7 and 21, increased NK cells on day 7, increased macrophages on day 7 and increased MHC Class IIhi macrophages on days 7 and 21. In the adaptive response, CD4+ and CD8+ T cells were decreased on day 7 and increased on day 21. CD4+ T cell subsets showed increased CD4+Foxp3+ T cells on day 7 and increased CD4+Tbet+ T cells on day 21. B lymphocytes were lower at all time points. Together, this suggests that VAD affects multiple cell populations in both the innate and adaptive immune responses to viral infection in the lung, Supported by Grants from Sigma Xi Grant in Aid of Research, Saint Louis University College of Arts and Sciences Knoedler Award, and Saint Louis University College of Arts and Sciences Graduate Undergraduate Award.