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Grant Abstract

Grant Number: 2R01DK041479-23A1
PI Name: Ross
Project Title: Retinoid Nutritional Status and Immune Function

Abstract: DESCRIPTION (provided by applicant): At birth, the concentrations of vitamin A (VA) in liver and plasma are much lower than in older children and well-fed adults. Vitamin A may therefore be a rate-limiting nutrient at this life stage. This application focuses on the interaction in earl life of VA supplementation and immune function. Our central hypothesis is: In VA-marginal neonates, VA supplementation will be protective against Streptococcus pneumoniae infection, through an increase in favorable innate and adaptive immune responses, and a reduction in excessive tissue-destructive inflammatory responses. Reciprocally, we will test whether pneumonia infection alters the ability of the neonate to store and mobilize VA. Currently, scientific evidence for VA supplementation in neonates is very limited. We will use a neonatal mouse model to test whether VA supplementation early in life, combined with immunization, regulates the lung's innate and adaptive immune response to S. pneumoniae infection. Reciprocally, infection may affect the transport and metabolism of VA, due to reduced hepatic production of retinol-binding protein, RBP. Our specific aims address 1) the response to infection and 2) infection-induced alterations in retinol metabolism. The outcome of this research will be a better understanding of neonatal retinol metabolism and VA utilization in early life, which is expected to help make better public health decisions regarding VA supplementation in neonates. PUBLIC HEALTH RELEVANCE: A nutritional deficiency of vitamin A (VA) impairs immune response, which in turn increases severity of infectious diseases. Vitamin A supplementation has become widely used in the developing world to reduce under 5-y mortality. However, little is known about how VA affects immunity and lung health in the neonatal period. We will investigate VA supplementation and antibody production, relevant to lung health in humans, in a neonatal mouse model of S. pneumoniae infection. Evidence gained from our basic studies is expected to fill knowledge gaps concerning the role of VA in neonatal and young child health.

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