MOLECULAR CLONING OF THE SWINE IL-4 RECEPTOR AND IL-13 RECEPTOR ALPHA 1 CHAINS: EFFECTS OF EXPERIMENTAL TOXOPLASMA GONDII, ASCARIS SUUM AND TRICHURIS SUIS INFECTIONS ON TISSUE MRNA LEVELS

Authors: Zarlenga, Dante; Dawson, Harry; KRINGEL, HELENE - ROYAL VET AND AG UNIV; Solano-Aguilar, Gloria; Urban, Joseph

Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/29/2004
Publication Date: 7/21/2004
Citation: Zarlenga, D.S., Dawson, H.D., Kringel, H., Solano Aguilar, G., Urban Jr, J.F. 2004. Molecular cloning of the swine IL-4 receptor and IL-13 receptor alpha 1 chains: effects of experimental toxoplasma gondii, ascaris suum and trichuris suis infections on tissue mrna levels. Veterinary Immunology and Immunopathology 101(3-4):223-234.

Interpretive Summary: Parasitic infections in food animals result in specific and characteristic changes in the host immune responses. Two important immune related molecules known to be involved in regulating the infection process are IL-4 and IL-13. To date, no work has been performed on the corresponding swine receptor molecules so important in transducing the intracellular signals which in turn mediate the response. Herein, we present the cloning of the swine (sw) IL-4R' and swIL-13R'1 genes and examine alterations in structure and in gene expression in pigs infected with classes of parasites known to elicit predictable but distinct host responses. Results show substantially different responses at the site of infection than those predicted from conventional wisdom and murine models, where these receptor genes are up-regulated in protozoan infections and down-regulated in nematode infections. Data presented here demonstrate the importance of studying both biochemical and physiological aspects of receptor/cytokine relationships in deciphering host responses to infection, and the inability of rodent models to be a panacea for predicting immune responses in large animal systems. Furthermore, understanding interactions involving immune modulation that take place at the cell surface and subsequently effect signal transduction may offer greater insight into the mechanisms associated with host immune responses than those ascertained by monitoring circulating levels of effector molecules only. These data will be critical in developing antagonistic and/or agonistic immune related reagents capable of modulating host responses to infection.

Technical Abstract: IL-4 and IL-13 are multi-functional cytokines with overlapping roles in the host defense against infection. Equally important in the regulation of IL-4 and IL-13 are their associated receptors. Though their functional receptor complexes and signaling pathways are intricate and in some cases share common elements, the specificity of the responses nonetheless reside in the structure and binding of the '-chain components. This report presents the cloning and sequence analysis of the swine receptors IL-4R' and IL-13R'1. Pairwise alignment of predicted amino-acid sequences indicates that the swine IL-13R'1 is 86%, 83% and 72% similar to canine, human and mouse sequences, respectively. Amino acid sequence conservation is appreciably lower between the swine IL-4R' sequence and those from equine (72%), human (66%) and mouse (49%); however, noteworthy similarities were observed in their overall predicted secondary structures. Relative levels of receptor mRNA in tissues from swine experimentally infected with protozoan (Toxoplasma gondii) or nematode (Ascaris suum, Trichuris suis) parasites known to induce Th1 or Th2 host responses, respectively, were measured by real-time PCR. Results indicated that within 14 days following infection, overall mRNA levels for IL-4R' and IL-13R'1 were reduced in A. suum infected animals and elevated in T. gondii infected animals. Conversely, mRNA levels of swIL-4R' and swIL-13R'1 in T. suis infected animals varied coincidentally with the course of the infection and the location of the tissue analyzed.