Localized Th1-, Th2-, T Regulatory Cell-, and Inflammation-Associated Hepatic and Pulmonary Immune Responses inAscaris suum-Infected Swine Are Increased by Retinoic Acid

Harry Dawson,Joseph F Urban,Ethiopia Beshah,Sebastian Botero,Eudora Jones,Vandana Vangimalla,Madeline Beal,Gloria Solano-Aguilar

doi:10.1128/iai.00827-07

Harry Dawson, Joseph F Urban + Show 6 more

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Pigs infected with Ascaris suum or controls were given 100 microg (low-dose) or 1,000 microg (high-dose) all-trans retinoic acid (ATRA)/kg body weight in corn oil or corn oil alone per os on days after inoculation (DAI) -1, +1, and +3 with infective eggs. Treatment with ATRA increased interleukin 4 (IL4) and IL12p70 in plasma of infected pigs at 7 DAI and augmented bronchoalveolar lavage (BAL) eosinophilia observed at 7 and 14 DAI. To explore potential molecular mechanisms underlying these observations, a quantitative real-time reverse transcription (RT)-PCR array was used to examine mRNA expression in tissue. Ascaris-infected pigs had increased levels of liver mRNA for T-helper-2 (Th2)-associated cytokines, mast cell markers, and T regulatory (Treg) cells, while infected pigs given ATRA had higher IL4, IL13, CCL11, CCL26, CCL17, CCL22, and TPSB1 expression. Gene expression for Th1-associated markers (IFNG, IL12B, and TBX21), the CXCR3 ligand (CXCL9), IL1B, and the putative Treg marker TNFRSF18 was also increased. Expression of IL4, IL13, IL1B, IL6, CCL11, and CCL26 was increased in the lungs of infected pigs treated with ATRA. To determine a putative cellular source of eosinophil chemoattractants, alveolar macrophages were treated with IL4 and/or ATRA in vitro. IL4 induced CCL11, CCL17, CCL22, and CCL26 mRNA, and ATRA increased the basal and IL4-stimulated expression of CCL17 and CCL22. Thus, ATRA augments a diverse Th1-, Th2-, Treg-, and inflammation-associated response in swine infected with A. suum, and the increased BAL eosinophilia may be related to enhanced induction of eosinophil chemokine activity by alveolar macrophages.

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Diet, Genomics and Immunology Laboratory, Beltsville Human Nutrition Research Center, ARS, USDA, Beltsville, Maryland 207051; Experimental Transplantation and Immunology Branch, NCI, NIH, Bethesda, Maryland 208922; and Clinical Center, NIH, Bethesda, Maryland 208923
Real-time PCR detection of mRNA expression (CT values) for CCR3 and CCR4 ligands and selected genes associated with eosinophils, mast cells, and inflammation in the liver at 7 and 14 days after inoculation was evaluated by one-way analysis of variance (ANOVA). n-fold changes relative to results for control pigs are designated by color differences, defined in the figure insert, and statistical significance by A (P Ͻ 0.05) or B (P Ͻ 0.01)
Our studies demonstrated that oral all-trans retinoic acid (ATRA) suppledetection of mRNA expression (CT values) for selected genes associated with Th1 or Th2 cells or T regulatory (Treg) in the livers of pigs infected with A. suum and treated with two different doses of ATRA is shown

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Genomics and Immunology Laboratory, Beltsville Human Nutrition Research Center, ARS, USDA, Beltsville, Maryland 207051; Experimental Transplantation and Immunology Branch, NCI, NIH, Bethesda, Maryland 208922; and Clinical Center, NIH, Bethesda, Maryland 208923. Ascaris-infected pigs had increased levels of liver mRNA for T-helper-2 (Th2)-associated cytokines, mast cell markers, and T regulatory (Treg) cells, while infected pigs given ATRA had higher IL4, IL13, CCL11, CCL26, CCL17, CCL22, and TPSB1 expression. ATRA augments a diverse Th1-, Th2-, Treg-, and inflammation-associated response in swine infected with A. suum, and the increased BAL eosinophilia may be related to enhanced induction of eosinophil chemokine activity by alveolar macrophages. Ascaris suum antigens have been used to model localized allergic hypersensitivity and asthma in several different mammalian species, including pigs, because they elicit allergic symptoms similar to those manifested in humans infected with A. lumbricoides [45]. Vitamin A (VA) and VA-like retinoids modify Th1-, Th2-, and T regulatory (Treg)-associated immune responses in rodents and humans, but a definitive mechanism(s) of action is lacking. The morbidity and mortality associated with malaria and measles increased with VA deficiency (39a, 41b), and VA-supplemented children infected with enteropathogenic Escherichia coli had reduced fecal protein levels of IFN-␥ (26a, 26b)

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