Infection and Immunity, June 2009, p. 2576-2587, Vol. 77, No. 6
0019-9567/09/$08.00+0 doi:10.1128/IAI.00827-07
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Localized Th1-, Th2-, T Regulatory Cell-, and Inflammation-Associated Hepatic and Pulmonary Immune Responses in Ascaris suum-Infected Swine Are Increased by Retinoic Acid
,
Harry Dawson,1*
Gloria Solano-Aguilar,1
Madeline Beal,2
Ethiopia Beshah,1
Vandana Vangimalla,1
Eudora Jones,3
Sebastian Botero,1 and
Joseph F. Urban Jr.1
Diet, Genomics and Immunology Laboratory, Beltsville Human Nutrition Research Center, ARS, USDA, Beltsville, Maryland 20705,1 Experimental Transplantation and Immunology Branch, NCI, NIH, Bethesda, Maryland 20892,2 Clinical Center, NIH, Bethesda, Maryland 208923
Received 15 June 2007/ Returned for modification 17 July 2007/ Accepted 6 March 2009
Pigs infected with Ascaris suum or controls were given 100 µg (low-dose) or 1,000 µg (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.
* Corresponding author. Mailing address: Diet, Genomics, & Immunology Laboratory, Rm. 224, Bldg. 307C, Beltsville Human Nutrition Research Center, U.S. Department of Agriculture, BARC-East, 10300 Baltimore Ave., Beltsville, MD 20705. Phone: (301) 504-9412. Fax: (301) 504-9062. E-mail: Harry.Dawson{at}ars.usda.gov
Published ahead of print on 30 March 2009.
Supplemental material for this article may be found at http://iai.asm.org/.
Infection and Immunity, June 2009, p. 2576-2587, Vol. 77, No. 6
0019-9567/09/$08.00+0 doi:10.1128/IAI.00827-07
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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