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.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01DK041479-24
Application #
8699185
Study Section
Integrative Nutrition and Metabolic Processes Study Section (INMP)
Program Officer
Maruvada, Padma
Project Start
Project End
Budget Start
Budget End
Support Year
24
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Pennsylvania State University
Department
Nutrition
Type
Sch Allied Health Professions
DUNS #
City
University Park
State
PA
Country
United States
Zip Code
16802
Chen, Qiuyan; Ross, A Catharine (2015) All-trans-retinoic acid and CD38 ligation differentially regulate CD1d expression and α-galactosylceramide-induced immune responses. Immunobiology 220:32-41
McDaniel, Kaitlin L; Restori, Katherine H; Dodds, Jeffery W et al. (2015) Vitamin A-Deficient Hosts Become Nonsymptomatic Reservoirs of Escherichia coli-Like Enteric Infections. Infect Immun 83:2984-91
Chen, Q; Ross, A C (2015) α-Galactosylceramide stimulates splenic lymphocyte proliferation in vitro and increases antibody production in vivo in late neonatal-age mice. Clin Exp Immunol 179:188-96
Restori, Katherine H; McDaniel, Kaitlin L; Wray, Amanda E et al. (2014) Streptococcus pneumoniae-induced pneumonia and Citrobacter rodentium-induced gut infection differentially alter vitamin A concentrations in the lung and liver of mice. J Nutr 144:392-8
Zhang, Yao; Ross, A Catharine (2013) Retinoic acid and the transcription factor MafB act together and differentially to regulate aggrecan and matrix metalloproteinase gene expression in neonatal chondrocytes. J Cell Biochem 114:471-9
Wu, Lili; Ross, A Catharine (2013) Inflammation induced by lipopolysaccharide does not prevent the vitamin A and retinoic acid-induced increase in retinyl ester formation in neonatal rat lungs. Br J Nutr 109:1739-45
Chen, Qiuyan; Mosovsky, Kara L; Ross, A Catharine (2013) Retinoic acid and α-galactosylceramide regulate the expression of costimulatory receptors and transcription factors responsible for B cell activation and differentiation. Immunobiology 218:1477-87
Restori, Katherine H; Kennett, Mary J; Ross, A Catharine (2013) Immunization with pneumococcal polysaccharide serotype 3 and lipopolysaccharide modulates lung and liver inflammation during a virulent Streptococcus pneumoniae infection in mice. Clin Vaccine Immunol 20:639-50
Zhang, Yao; Wray, Amanda E; Ross, A Catharine (2012) Perinatal exposure to vitamin A differentially regulates chondrocyte growth and the expression of aggrecan and matrix metalloprotein genes in the femur of neonatal rats. J Nutr 142:649-54
Zhang, Y; Chen, Q; Ross, A C (2012) Retinoic acid and tumor necrosis factor-α induced monocytic cell gene expression is regulated in part by induction of transcription factor MafB. Exp Cell Res 318:2407-16

Showing the most recent 10 out of 65 publications