Harry Dawson | USDA Agricultural Research Service (original) (raw)

Papers by Harry Dawson

Research paper thumbnail of Future of biomedical, agricultural, and biological systems research using domesticated animals

Biology of Reproduction, 2022

Increased knowledge of reproduction and health of domesticated animals is integral to sustain and... more Increased knowledge of reproduction and health of domesticated animals is integral to sustain and improve global competitiveness of U.S. animal agriculture, understand and resolve complex animal and human diseases, and advance fundamental research in sciences that are critical to understanding mechanisms of action and identifying future targets for interventions. Historically, federal and state budgets have dwindled and funding for the United States Department of Agriculture (USDA) National Institute of Food and Agriculture (NIFA) competitive grants programs remained relatively stagnant from 1985 through 2010. This shortage in critical financial support for basic and applied research, coupled with the underappreciated knowledge of the utility of non-rodent species for biomedical research, hindered funding opportunities for research involving livestock and limited improvements in both animal agriculture and animal and human health. In 2010, the National Institutes of Health and USDA ...

Research paper thumbnail of Receptors for IL-13 in Murine Gut Differences in Localized Gene Expression of Functional Importance of Regional

Research paper thumbnail of Intestine during Nippostrongylus brasiliensis Receptor-1 Expression in Murine Small Immune Regulation of Protease-Activated

Research paper thumbnail of Development of real-time RT-PCR assays for porcine cytokine gene expression

Research paper thumbnail of Arginine and Immunity

Diet, Nutrition, and Immunity, 2018

Research paper thumbnail of The probiotic Bifidobacterium lactis (Bb12) modulates adipocyte size in pig model of juvenile obesity

Research paper thumbnail of Soy Formula Is Not Estrogenic and Does Not Result in Reproductive Toxicity in Male Piglets: Results from a Controlled Feeding Study

Nutrients, 2022

Soy infant formula which is fed to over half a million infants per year contains isoflavones such... more Soy infant formula which is fed to over half a million infants per year contains isoflavones such as genistein, which have been shown to be estrogenic at high concentrations. The developing testis is sensitive to estrogens, raising concern that the use of soy formulas may result in male reproductive toxicity. In the current study, male White-Dutch Landrace piglets received either sow milk (Sow), or were provided milk formula (Milk), soy formula (Soy), milk formula supplemented with 17-beta-estradiol (2 mg/kg/d) (M + E2) or supplemented with genistein (84 mg/L of diet; (M + G) from postnatal day 2 until day 21. E2 treatment reduced testis weight (p < 0.05) as percentage of body weight, significantly suppressed serum androgen concentrations, increased tubule area, Germ cell and Sertoli cell numbers (p < 0.05) relative to those of Sow or Milk groups. Soy formula had no such effects relative to Sow or Milk groups. mRNAseq revealed 103 differentially expressed genes in the M + E2 g...

Research paper thumbnail of Additional file 4: of The porcine translational research database: a manually curated, genomics and proteomics-based research resource

5′, ORF and 3′ end comparison of porcine and human mRNAs. 5′, ORF and 3′ end comparison of porcin... more 5′, ORF and 3′ end comparison of porcine and human mRNAs. 5′, ORF and 3′ end comparison of porcine and human mRNAs (XLSX 66 kb)

Research paper thumbnail of Transcriptome analysis reveals persistent effects of neonatal diet on small intestine gene expression profile in a porcine model

Research paper thumbnail of Fruit and Vegetable Supplemented Diet Modulates the Pig Transcriptome and Microbiome after a Two-Week Feeding Intervention

Nutrients, 2021

A study was conducted to determine the effects of a diet supplemented with fruits and vegetables ... more A study was conducted to determine the effects of a diet supplemented with fruits and vegetables (FV) on the host whole blood cell (WBC) transcriptome and the composition and function of the intestinal microbiome. Nine six-week-old pigs were fed a pig grower diet alone or supplemented with lyophilized FV equivalent to half the daily recommended amount prescribed for humans by the Dietary Guideline for Americans (DGA) for two weeks. Host transcriptome changes in the WBC were evaluated by RNA sequencing. Isolated DNA from the fecal microbiome was used for 16S rDNA taxonomic analysis and prediction of metabolomic function. Feeding an FV-supplemented diet to pigs induced differential expression of several genes associated with an increase in B-cell development and differentiation and the regulation of cellular movement, inflammatory response, and cell-to-cell signaling. Linear discriminant analysis effect size (LEfSe) in fecal microbiome samples showed differential increases in genera f...

Research paper thumbnail of Tissue-specific mechanisms of bile acid homeostasis and activation of FXR-FGF19 signaling in preterm and term neonatal pigs

American Journal of Physiology-Gastrointestinal and Liver Physiology, 2021

Our results show that the lower hepatic bile acid synthesis and ileum FXR-FGF19 pathway responsiv... more Our results show that the lower hepatic bile acid synthesis and ileum FXR-FGF19 pathway responsiveness to bile acids contribute to low-circulating FGF19 in preterm compared with term neonatal pigs. The molecular mechanism explaining immature or low-ileum FXR-FGF19 signaling may be linked to developmental patterning effects of GATA-4.

Research paper thumbnail of Male testicular development is affected by estrogens but not altered in neonatal piglets receiving soy infant formula

Research paper thumbnail of Colon transcriptome is modified by a dietary pattern/atorvastatin interaction in the Ossabaw pig

The Journal of Nutritional Biochemistry, 2021

Optimizing diet quality in conjunction with statin therapy is currently the most common approach ... more Optimizing diet quality in conjunction with statin therapy is currently the most common approach for coronary artery disease (CAD) risk management. Although effects on the cardiovascular system have been extensively investigated, little is known about the effect of these interventions in the colon and subsequent associations with CAD progression. To address this gap, Ossabaw pigs were randomly allocated to receive, for a six-month period, isocaloric amounts of either a heart healthy-type diet (HHD; high in unrefined carbohydrate, unsaturated fat, fiber, supplemented with fish oil, and low in cholesterol) or a Western-type diet (WD; high in refined carbohydrate, saturated fat and cholesterol, and low in fiber), without or with atorvastatin therapy. At the end of the intervention period, colon samples were harvested, mucosa fraction isolated, and RNA sequenced. Gene differential expression and enrichment analyses indicated that dietary patterns and atorvastatin therapy differentially altered gene expression, with diet-statin interactions. Atorvastatin had a more profound effect on differential gene expression than diet. In pigs not receiving atorvastatin, the WD upregulated "LXR/RXR Activation" pathway compared to pigs fed the HHD. Enrichment analysis indicated that atorvastatin therapy lowered inflammatory status in the HHD-fed pigs, whereas it induced a colitis-like gene expression phenotype in the WD-fed pigs. No significant association was identified between gene expression phenotypes and severity of atherosclerotic lesions in the left anterior descending-left circumflex bifurcation artery. These data suggested diet quality modulated the response to atorvastatin therapy in colonic mucosa, and these effects were unrelated to atherosclerotic lesion development.

Research paper thumbnail of Formula Diet Alters the Ileal Metagenome and Transcriptome at Weaning and during the Postweaning Period in a Porcine Model

mSystems, 2020

Exclusive human milk (HM) breastfeeding for the first 6 months of age in infants is recommended t... more Exclusive human milk (HM) breastfeeding for the first 6 months of age in infants is recommended to improve health outcomes during early life and beyond. When women are unable to provide sufficient HM, milk formula (MF) is often recommended as a complementary or alternative source of nutrition. Previous studies in piglets demonstrated that MF alters the gut microbiome and induces inflammatory cytokine production. The links between MF feeding, gut microbiome, and inflammation status are unclear due to challenges associated with the collection of intestinal samples from human infants. The current report provides the first insight into MF-microbiome-inflammation connections in the small intestine compared with HM feeding using a porcine model. The present results showed that, compared with HM, MF might impact immune function through the induction of ileal inflammation, apoptosis, and tight junction disruptions and likely compromised immune defense against pathogen detection in the small...

Research paper thumbnail of Application of RNA-seq transcriptomic analysis to reproductive physiology of the pig: Insights into differential trophoblast function within the late gestation porcine placenta

Bioscientifica Proceedings, 2019

(USDA) prohibits discrimination in all its programs and activities on the basis of race, color, n... more (USDA) prohibits discrimination in all its programs and activities on the basis of race, color, national origin, age, disability, and where applicable, sex, marital status, familial status, parental status, religion, sexual orientation, genetic information, political beliefs, reprisal, or because all or part of an individual's income is derived from any public assistance program. (Not all prohibited bases apply to all programs.) Persons with disabilities who require alternative means for communication of program information (Braille, large print, audiotape, etc.

Research paper thumbnail of Potentiation of IL-4 Signaling by Retinoic Acid in Intestinal Epithelial Cells and Macrophages—Mechanisms and Targets

Frontiers in Immunology, 2020

We previously demonstrated that IL4, IL13, CLCA1, and CCL26 mRNA were significantly upregulated i... more We previously demonstrated that IL4, IL13, CLCA1, and CCL26 mRNA were significantly upregulated in the lungs of pigs given a low dose of all trans-retinoic acid (ATRA) and infected with Ascaris suum. We also demonstrated that in vitro ATRA induced a state of partial alternative activation in porcine macrophages (Mϕs) and amplified certain aspects of M2a activation induced by IL-4. Given these results, we tested the effect of ATRA on IL-4 responses in two porcine intestinal epithelial cell lines, IPEC1 and IPEC-J2 and observed that ATRA increased mRNA for the IL-4 receptor alpha chain. ATRA also increased IL-4 induced phosphorylation of signal transducer and activator of transcription 6 (STAT6) and mRNA expression of the chloride channel, calcium activated, family member 1 (CLCA1), important for mucus formation, and chemokine (C-C motif) ligand 26 (CCL26), a potent eosinophil chemoattractant. We extended these findings to human Mϕ THP-1 cells and showed that ATRA synergistically increased IL-4-induced CCL2, CCL13, and CCL26 mRNA and protein levels. Transglutaminase 2 mRNA, protein, and enzyme activity were synergistically induced in THP-1 cells pretreated with ATRA and then treated with IL-4, thus, ATRA increased signaling in response to IL-4 in porcine epithelial cells and porcine and human Mϕs. Given the prevalence of allergic and parasitic diseases worldwide and the close similarities in the porcine and human immune responses, these findings have important implications for the nutritional regulation of allergic inflammation at mucosal surfaces.

Research paper thumbnail of Pomegranate peel extract alters the microbiome in mice and dysbiosis caused by Citrobacter rodentium infection

Food Science & Nutrition, 2019

Fruits are rich sources of polyphenols and antioxidants. Extracts of a variety of fruits have bee... more Fruits are rich sources of polyphenols and antioxidants. Extracts of a variety of fruits have been tested for their ability to counteract health conditions including obesity, diabetes, and colitis. Grape and apple polyphenols improved the outcome of dextran sulfate sodium (DSS)-induced colitis in rats (Boussenna et al., 2016; Denis et al., 2016). Fruit extracts, rich in polyphenols, including pomegranate, stimulated the growth of Akkermansia municiphila

Research paper thumbnail of The regulatory actions of retinoic acid on M2 polarization of porcine macrophages

Developmental & Comparative Immunology, 2019

We previously demonstrated that the most bioactive vitamin A metabolite, all-trans retinoic acid ... more We previously demonstrated that the most bioactive vitamin A metabolite, all-trans retinoic acid (ATRA), increased T helper 2-associated responses induced in pigs by infection with the parasitic nematode Ascaris suum We also showed that ATRA potentiated the mRNA expression of several IL-4 induced chemokines (chemokine (C-C motif) ligand 11 [(CCL11), CCL17, CCL22 and CCL26] associated with alternative activation (M2a) in porcine macrophages in vitro. Herein, several mechanisms whereby ATRA affects IL-4 signaling are profiled using large-scale real time PCR and RNA-Seq analysis. Twenty-three genes associated with M2a markers in other species were independently upregulated by both IL-4 and ATRA, including the adenosine receptor A2B (ADORA2B), cysteinyl leukotriene receptor 2 (CYSLTR2) and the vitamin D receptor (VDR). ATRA synergistically enhanced IL-4 up-regulation of Hepatitis A virus cellular receptor 2 (HAVCR2) and transglutaminase 2 (TGM2) and further repressed IL-4 down-regulated CD163 and Cytochrome b-245, beta polypeptide (CYBB) mRNA. Macrophages treated with ATRA exhibited a dose-dependent reduction in phagocytosis of opsonized Staphylococcus aureus. In addition, the combination of IL-4 and ATRA upregulated the anti-inflammatory protein, IL-1R antagonist (IL1RN) and TGM2. These data indicate that ATRA induces a state of partial alternative activation in porcine macrophages, and amplifies certain aspects of M2a activation induced by IL-4. Given the prevalence of allergic and parasitic diseases worldwide and the close similarities in the porcine and human immune responses, these findings have important implications for the nutritional regulation of allergic inflammation at mucosal surfaces.

Research paper thumbnail of Chronic Marginal Vitamin A Status Affects the Distribution and Function of T Cells and Natural T Cells in Aging Lewis Rats

The Journal of Nutrition, 1999

Although both vitamin A (VA) deficiency and aging are independently associated with alterations i... more Although both vitamin A (VA) deficiency and aging are independently associated with alterations in immune function, the effects of marginal VA status or VA supplementation on the immune system during aging were not studied. A long-term dietary study was conducted in a rat model of aging to quantify changes in T-cell populations in blood and spleen, including T-cells bearing a marker of natural killer (NKT) cells. The study included nine treatment groups [three levels of dietary VA: marginal (0.35 RE/kg diet), control (4.0 RE/kg diet), and supplemented (50 RE/kg diet); and three age groups: young (2-3 mo), middle-aged (8-10 mo), and old 20-22 mo); diets were fed continuously from weaning to the end of the study period. CD3 ϩ /CD4 ϩ T-cells decreased in percentage and number in blood with age, CD8 ϩ cells increased (%), and the CD4/CD8 ratio decreased. Conversely, aging was associated with increased NKT cells (phenotype CD3 intermediate /NKR-P1 ϩ). Based on regression analysis of flow cytometry data, the phenotype of most NKT cells was CD3 intermediate /NKR-P1 ϩ /CD28 Ϫ. NKT cells, which are most likely of extrathymic origin, accounted for most of the decrease in the CD4/CD8 ratio. Marginal VA status, particularly in older rats, was associated with increases in the percentage of CD8 ϩ T cells, percentage and number of NKT cells, and peripheral blood cell anti-CD3⑀-stimulated proliferative response, and decreases in the CD4/CD8 T-cell ratio and splenic cell interleukin-2 production. These differences and the reciprocal changes observed for NKT cells vs. T-and classical NK cells in aging VA-marginal rats suggest that low VA status during aging may increase the risk of infectious or neoplastic diseases that require a normal balance of T-cell or NK-cell responses.

Research paper thumbnail of A Comparative Assessment of the Pig, Mouse and Human Genomes

The Minipig in Biomedical Research, 2011

Research paper thumbnail of Future of biomedical, agricultural, and biological systems research using domesticated animals

Biology of Reproduction, 2022

Increased knowledge of reproduction and health of domesticated animals is integral to sustain and... more Increased knowledge of reproduction and health of domesticated animals is integral to sustain and improve global competitiveness of U.S. animal agriculture, understand and resolve complex animal and human diseases, and advance fundamental research in sciences that are critical to understanding mechanisms of action and identifying future targets for interventions. Historically, federal and state budgets have dwindled and funding for the United States Department of Agriculture (USDA) National Institute of Food and Agriculture (NIFA) competitive grants programs remained relatively stagnant from 1985 through 2010. This shortage in critical financial support for basic and applied research, coupled with the underappreciated knowledge of the utility of non-rodent species for biomedical research, hindered funding opportunities for research involving livestock and limited improvements in both animal agriculture and animal and human health. In 2010, the National Institutes of Health and USDA ...

Research paper thumbnail of Receptors for IL-13 in Murine Gut Differences in Localized Gene Expression of Functional Importance of Regional

Research paper thumbnail of Intestine during Nippostrongylus brasiliensis Receptor-1 Expression in Murine Small Immune Regulation of Protease-Activated

Research paper thumbnail of Development of real-time RT-PCR assays for porcine cytokine gene expression

Research paper thumbnail of Arginine and Immunity

Diet, Nutrition, and Immunity, 2018

Research paper thumbnail of The probiotic Bifidobacterium lactis (Bb12) modulates adipocyte size in pig model of juvenile obesity

Research paper thumbnail of Soy Formula Is Not Estrogenic and Does Not Result in Reproductive Toxicity in Male Piglets: Results from a Controlled Feeding Study

Nutrients, 2022

Soy infant formula which is fed to over half a million infants per year contains isoflavones such... more Soy infant formula which is fed to over half a million infants per year contains isoflavones such as genistein, which have been shown to be estrogenic at high concentrations. The developing testis is sensitive to estrogens, raising concern that the use of soy formulas may result in male reproductive toxicity. In the current study, male White-Dutch Landrace piglets received either sow milk (Sow), or were provided milk formula (Milk), soy formula (Soy), milk formula supplemented with 17-beta-estradiol (2 mg/kg/d) (M + E2) or supplemented with genistein (84 mg/L of diet; (M + G) from postnatal day 2 until day 21. E2 treatment reduced testis weight (p < 0.05) as percentage of body weight, significantly suppressed serum androgen concentrations, increased tubule area, Germ cell and Sertoli cell numbers (p < 0.05) relative to those of Sow or Milk groups. Soy formula had no such effects relative to Sow or Milk groups. mRNAseq revealed 103 differentially expressed genes in the M + E2 g...

Research paper thumbnail of Additional file 4: of The porcine translational research database: a manually curated, genomics and proteomics-based research resource

5′, ORF and 3′ end comparison of porcine and human mRNAs. 5′, ORF and 3′ end comparison of porcin... more 5′, ORF and 3′ end comparison of porcine and human mRNAs. 5′, ORF and 3′ end comparison of porcine and human mRNAs (XLSX 66 kb)

Research paper thumbnail of Transcriptome analysis reveals persistent effects of neonatal diet on small intestine gene expression profile in a porcine model

Research paper thumbnail of Fruit and Vegetable Supplemented Diet Modulates the Pig Transcriptome and Microbiome after a Two-Week Feeding Intervention

Nutrients, 2021

A study was conducted to determine the effects of a diet supplemented with fruits and vegetables ... more A study was conducted to determine the effects of a diet supplemented with fruits and vegetables (FV) on the host whole blood cell (WBC) transcriptome and the composition and function of the intestinal microbiome. Nine six-week-old pigs were fed a pig grower diet alone or supplemented with lyophilized FV equivalent to half the daily recommended amount prescribed for humans by the Dietary Guideline for Americans (DGA) for two weeks. Host transcriptome changes in the WBC were evaluated by RNA sequencing. Isolated DNA from the fecal microbiome was used for 16S rDNA taxonomic analysis and prediction of metabolomic function. Feeding an FV-supplemented diet to pigs induced differential expression of several genes associated with an increase in B-cell development and differentiation and the regulation of cellular movement, inflammatory response, and cell-to-cell signaling. Linear discriminant analysis effect size (LEfSe) in fecal microbiome samples showed differential increases in genera f...

Research paper thumbnail of Tissue-specific mechanisms of bile acid homeostasis and activation of FXR-FGF19 signaling in preterm and term neonatal pigs

American Journal of Physiology-Gastrointestinal and Liver Physiology, 2021

Our results show that the lower hepatic bile acid synthesis and ileum FXR-FGF19 pathway responsiv... more Our results show that the lower hepatic bile acid synthesis and ileum FXR-FGF19 pathway responsiveness to bile acids contribute to low-circulating FGF19 in preterm compared with term neonatal pigs. The molecular mechanism explaining immature or low-ileum FXR-FGF19 signaling may be linked to developmental patterning effects of GATA-4.

Research paper thumbnail of Male testicular development is affected by estrogens but not altered in neonatal piglets receiving soy infant formula

Research paper thumbnail of Colon transcriptome is modified by a dietary pattern/atorvastatin interaction in the Ossabaw pig

The Journal of Nutritional Biochemistry, 2021

Optimizing diet quality in conjunction with statin therapy is currently the most common approach ... more Optimizing diet quality in conjunction with statin therapy is currently the most common approach for coronary artery disease (CAD) risk management. Although effects on the cardiovascular system have been extensively investigated, little is known about the effect of these interventions in the colon and subsequent associations with CAD progression. To address this gap, Ossabaw pigs were randomly allocated to receive, for a six-month period, isocaloric amounts of either a heart healthy-type diet (HHD; high in unrefined carbohydrate, unsaturated fat, fiber, supplemented with fish oil, and low in cholesterol) or a Western-type diet (WD; high in refined carbohydrate, saturated fat and cholesterol, and low in fiber), without or with atorvastatin therapy. At the end of the intervention period, colon samples were harvested, mucosa fraction isolated, and RNA sequenced. Gene differential expression and enrichment analyses indicated that dietary patterns and atorvastatin therapy differentially altered gene expression, with diet-statin interactions. Atorvastatin had a more profound effect on differential gene expression than diet. In pigs not receiving atorvastatin, the WD upregulated "LXR/RXR Activation" pathway compared to pigs fed the HHD. Enrichment analysis indicated that atorvastatin therapy lowered inflammatory status in the HHD-fed pigs, whereas it induced a colitis-like gene expression phenotype in the WD-fed pigs. No significant association was identified between gene expression phenotypes and severity of atherosclerotic lesions in the left anterior descending-left circumflex bifurcation artery. These data suggested diet quality modulated the response to atorvastatin therapy in colonic mucosa, and these effects were unrelated to atherosclerotic lesion development.

Research paper thumbnail of Formula Diet Alters the Ileal Metagenome and Transcriptome at Weaning and during the Postweaning Period in a Porcine Model

mSystems, 2020

Exclusive human milk (HM) breastfeeding for the first 6 months of age in infants is recommended t... more Exclusive human milk (HM) breastfeeding for the first 6 months of age in infants is recommended to improve health outcomes during early life and beyond. When women are unable to provide sufficient HM, milk formula (MF) is often recommended as a complementary or alternative source of nutrition. Previous studies in piglets demonstrated that MF alters the gut microbiome and induces inflammatory cytokine production. The links between MF feeding, gut microbiome, and inflammation status are unclear due to challenges associated with the collection of intestinal samples from human infants. The current report provides the first insight into MF-microbiome-inflammation connections in the small intestine compared with HM feeding using a porcine model. The present results showed that, compared with HM, MF might impact immune function through the induction of ileal inflammation, apoptosis, and tight junction disruptions and likely compromised immune defense against pathogen detection in the small...

Research paper thumbnail of Application of RNA-seq transcriptomic analysis to reproductive physiology of the pig: Insights into differential trophoblast function within the late gestation porcine placenta

Bioscientifica Proceedings, 2019

(USDA) prohibits discrimination in all its programs and activities on the basis of race, color, n... more (USDA) prohibits discrimination in all its programs and activities on the basis of race, color, national origin, age, disability, and where applicable, sex, marital status, familial status, parental status, religion, sexual orientation, genetic information, political beliefs, reprisal, or because all or part of an individual's income is derived from any public assistance program. (Not all prohibited bases apply to all programs.) Persons with disabilities who require alternative means for communication of program information (Braille, large print, audiotape, etc.

Research paper thumbnail of Potentiation of IL-4 Signaling by Retinoic Acid in Intestinal Epithelial Cells and Macrophages—Mechanisms and Targets

Frontiers in Immunology, 2020

We previously demonstrated that IL4, IL13, CLCA1, and CCL26 mRNA were significantly upregulated i... more We previously demonstrated that IL4, IL13, CLCA1, and CCL26 mRNA were significantly upregulated in the lungs of pigs given a low dose of all trans-retinoic acid (ATRA) and infected with Ascaris suum. We also demonstrated that in vitro ATRA induced a state of partial alternative activation in porcine macrophages (Mϕs) and amplified certain aspects of M2a activation induced by IL-4. Given these results, we tested the effect of ATRA on IL-4 responses in two porcine intestinal epithelial cell lines, IPEC1 and IPEC-J2 and observed that ATRA increased mRNA for the IL-4 receptor alpha chain. ATRA also increased IL-4 induced phosphorylation of signal transducer and activator of transcription 6 (STAT6) and mRNA expression of the chloride channel, calcium activated, family member 1 (CLCA1), important for mucus formation, and chemokine (C-C motif) ligand 26 (CCL26), a potent eosinophil chemoattractant. We extended these findings to human Mϕ THP-1 cells and showed that ATRA synergistically increased IL-4-induced CCL2, CCL13, and CCL26 mRNA and protein levels. Transglutaminase 2 mRNA, protein, and enzyme activity were synergistically induced in THP-1 cells pretreated with ATRA and then treated with IL-4, thus, ATRA increased signaling in response to IL-4 in porcine epithelial cells and porcine and human Mϕs. Given the prevalence of allergic and parasitic diseases worldwide and the close similarities in the porcine and human immune responses, these findings have important implications for the nutritional regulation of allergic inflammation at mucosal surfaces.

Research paper thumbnail of Pomegranate peel extract alters the microbiome in mice and dysbiosis caused by Citrobacter rodentium infection

Food Science & Nutrition, 2019

Fruits are rich sources of polyphenols and antioxidants. Extracts of a variety of fruits have bee... more Fruits are rich sources of polyphenols and antioxidants. Extracts of a variety of fruits have been tested for their ability to counteract health conditions including obesity, diabetes, and colitis. Grape and apple polyphenols improved the outcome of dextran sulfate sodium (DSS)-induced colitis in rats (Boussenna et al., 2016; Denis et al., 2016). Fruit extracts, rich in polyphenols, including pomegranate, stimulated the growth of Akkermansia municiphila

Research paper thumbnail of The regulatory actions of retinoic acid on M2 polarization of porcine macrophages

Developmental & Comparative Immunology, 2019

We previously demonstrated that the most bioactive vitamin A metabolite, all-trans retinoic acid ... more We previously demonstrated that the most bioactive vitamin A metabolite, all-trans retinoic acid (ATRA), increased T helper 2-associated responses induced in pigs by infection with the parasitic nematode Ascaris suum We also showed that ATRA potentiated the mRNA expression of several IL-4 induced chemokines (chemokine (C-C motif) ligand 11 [(CCL11), CCL17, CCL22 and CCL26] associated with alternative activation (M2a) in porcine macrophages in vitro. Herein, several mechanisms whereby ATRA affects IL-4 signaling are profiled using large-scale real time PCR and RNA-Seq analysis. Twenty-three genes associated with M2a markers in other species were independently upregulated by both IL-4 and ATRA, including the adenosine receptor A2B (ADORA2B), cysteinyl leukotriene receptor 2 (CYSLTR2) and the vitamin D receptor (VDR). ATRA synergistically enhanced IL-4 up-regulation of Hepatitis A virus cellular receptor 2 (HAVCR2) and transglutaminase 2 (TGM2) and further repressed IL-4 down-regulated CD163 and Cytochrome b-245, beta polypeptide (CYBB) mRNA. Macrophages treated with ATRA exhibited a dose-dependent reduction in phagocytosis of opsonized Staphylococcus aureus. In addition, the combination of IL-4 and ATRA upregulated the anti-inflammatory protein, IL-1R antagonist (IL1RN) and TGM2. These data indicate that ATRA induces a state of partial alternative activation in porcine macrophages, and amplifies certain aspects of M2a activation induced by IL-4. Given the prevalence of allergic and parasitic diseases worldwide and the close similarities in the porcine and human immune responses, these findings have important implications for the nutritional regulation of allergic inflammation at mucosal surfaces.

Research paper thumbnail of Chronic Marginal Vitamin A Status Affects the Distribution and Function of T Cells and Natural T Cells in Aging Lewis Rats

The Journal of Nutrition, 1999

Although both vitamin A (VA) deficiency and aging are independently associated with alterations i... more Although both vitamin A (VA) deficiency and aging are independently associated with alterations in immune function, the effects of marginal VA status or VA supplementation on the immune system during aging were not studied. A long-term dietary study was conducted in a rat model of aging to quantify changes in T-cell populations in blood and spleen, including T-cells bearing a marker of natural killer (NKT) cells. The study included nine treatment groups [three levels of dietary VA: marginal (0.35 RE/kg diet), control (4.0 RE/kg diet), and supplemented (50 RE/kg diet); and three age groups: young (2-3 mo), middle-aged (8-10 mo), and old 20-22 mo); diets were fed continuously from weaning to the end of the study period. CD3 ϩ /CD4 ϩ T-cells decreased in percentage and number in blood with age, CD8 ϩ cells increased (%), and the CD4/CD8 ratio decreased. Conversely, aging was associated with increased NKT cells (phenotype CD3 intermediate /NKR-P1 ϩ). Based on regression analysis of flow cytometry data, the phenotype of most NKT cells was CD3 intermediate /NKR-P1 ϩ /CD28 Ϫ. NKT cells, which are most likely of extrathymic origin, accounted for most of the decrease in the CD4/CD8 ratio. Marginal VA status, particularly in older rats, was associated with increases in the percentage of CD8 ϩ T cells, percentage and number of NKT cells, and peripheral blood cell anti-CD3⑀-stimulated proliferative response, and decreases in the CD4/CD8 T-cell ratio and splenic cell interleukin-2 production. These differences and the reciprocal changes observed for NKT cells vs. T-and classical NK cells in aging VA-marginal rats suggest that low VA status during aging may increase the risk of infectious or neoplastic diseases that require a normal balance of T-cell or NK-cell responses.

Research paper thumbnail of A Comparative Assessment of the Pig, Mouse and Human Genomes

The Minipig in Biomedical Research, 2011