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)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK041479-23A1
Application #
8504172
Study Section
Integrative Nutrition and Metabolic Processes Study Section (INMP)
Program Officer
Maruvada, Padma
Project Start
1989-04-01
Project End
2016-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
23
Fiscal Year
2013
Total Cost
$325,163
Indirect Cost
$107,663
Name
Pennsylvania State University
Department
Nutrition
Type
Schools of Allied Health Profes
DUNS #
003403953
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 ?-galactosylceramide-induced immune responses. Immunobiology 220:32-41
Ross, A Catharine (2012) Use of laboratory studies for the design, explanation, and validation of human micronutrient intervention studies. J Nutr 142:157S-60S
Wu, Yong; Chen, Qiuyan; Pai, Tongkun et al. (2011) All-trans-retinoic acid and Erk1/2 signaling synergistically regulate the expression of CD300B in human monocytic cells. Cell Immunol 268:68-78
Ross, A Catharine; Cifelli, Christopher J; Zolfaghari, Reza et al. (2011) Multiple cytochrome P-450 genes are concomitantly regulated by vitamin A under steady-state conditions and by retinoic acid during hepatic first-pass metabolism. Physiol Genomics 43:57-67
Chen, Qiuyan; Mosovsky, Kara L; Ross, A Catharine (2011) Retinoic acid and ?-galactosylceramide differentially regulate B cell activation in vitro and augment antibody production in vivo. Clin Vaccine Immunol 18:1015-20
Wu, Lili; Ross, A Catharine (2010) Acidic retinoids synergize with vitamin A to enhance retinol uptake and STRA6, LRAT, and CYP26B1 expression in neonatal lung. J Lipid Res 51:378-87
Ross, A Catharine (2010) Diet in vitamin A research. Methods Mol Biol 652:295-313
Ma, Yifan; Ross, A Catharine (2009) Toll-like receptor 3 ligand and retinoic acid enhance germinal center formation and increase the tetanus toxoid vaccine response. Clin Vaccine Immunol 16:1476-84
Ross, A Catharine; Chen, Qiuyan; Ma, Yifan (2009) Augmentation of antibody responses by retinoic acid and costimulatory molecules. Semin Immunol 21:42-50
Sankaranarayanan, Sandhya; Ma, Yifan; Bryson, Mary C et al. (2007) Neonatal-age treatment with vitamin A delays postweaning vitamin A deficiency and increases the antibody response to T-cell dependent antigens in young adult rats fed a vitamin A-deficient diet. J Nutr 137:1229-35

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