Altered cytokine and chemokine profiles in the lungs of vitamin A deficient mice with respiratory syncytial virus infection

Abstract

Abstract Human respiratory syncytial virus (RSV) is a leading cause of severe acute lower respiratory tract disease worldwide in infants and young children. Epidemiologically, low levels of vitamin A (VA) are known to increase susceptibility to severe respiratory infection. However, little is known regarding how VA impacts lung immune function, specifically during RSV infection. Here, we investigated the impact of VA deficiency (VAD) on innate immunity in the lungs following RSV infection using a BALB/c mouse model. Groups of VA sufficient (VAS) and VAD, 6 to 8-week-old mice were intranasally infected with RSV, and lung tissues were collected at 3, 4, and 8 days post-infection for evaluation of vitamin A status, flow cytometry for innate immune populations, and Luminex bead-based multiplex assays for inflammatory cytokines. Acute RSV infection negatively impacted lung VA status in vitamin-replete mice. Although no differences in morbidity were observed between treatment groups, VAD mice had more neutrophils recruited to the lungs. VAD also altered the phenotype of γδ T cell populations in the lung, resulting in significantly increased frequencies of CD27+ γδ T cells, and fewer CD27 negative γδ T cells compared to VAS mice. Moreover, cytokine and chemokine production was altered in the lung of VAD animals after RSV infection, with reduced production of IL-1β, IL-6, IL-17, and KC (CXCL1). These results suggest that VAD alters the inflammatory environment in the lung, which may contribute to disease susceptibility. Future experiments will focus on further changes to the innate and adaptive immune systems in the lungs during VAD after RSV infection. Supported by Roy J. Carver Charitable Trust Grant #20-5306