|Ferman Ii, Geoffrey|
Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/7/2006
Publication Date: 1/15/2007
Citation: Bautista, E.M., Nfon, C., Ferman Ii, G.S., Golde, W.T. 2007. Il-13 replaces il-4 in development of monocyte derived dendritic cells (modc) of swine; the innate immune response of modc to toll-like receptor agonists. Veterinary Immunology and Immunopathology. 115:56-67. Interpretive Summary: Over the past several years, investigations in many mammalian species have identified the dendritic cell as a cell critical to the initiation and propagation of an immune response. These cells are the primary source of proteins termed cytokines that induce inflammation. Among the dendritic cell derived cytokines are the interferon molecules that can block viral replication and spread. In addition to rapid, nonspecific cytokine responses, dendritic cells also initiate the highly specific T cell responses that lead to both antibody and cellular immune responses. With such important characteristics, understanding the biology of dendritic cells has become a priority in studying immune responses of mammals to pathogens and vaccines. In swine, the generation of dendritic cells from peripheral blood has employed a tissue culture system that does not mimic the physiology of the animal. We now describe a new system, more closely following the biology of pigs, that yields a more appropriate population of dendritic cells for study. Analysis of the important immune functions of these cells is reported.
Technical Abstract: Dendritic cells (DCs) are a critical aspect of innate immune responses in addition to initiating adaptive immunity. In vitro generation of monocyte derived dendritic cells (MoDC) by culturing cells in IL-4 and GM-CSF has been reported for multiple species including swine. However, IL-4 is not a prominent cytokine detected in the periphery of common breeds of swine. In this study, we report the generation and characterization of porcine MoDC in vitro using porcine IL-13 and porcine GM-CSF. These cells have the predicted expression of Class II MHC and T cell costimulatory molecules, phagocytic capacity, and the ability to process and present antigen. Critically, porcine IL13/GM-CSF MoDC have the unique ability to stimulate a primary mixed lymphocyte response in vitro. The innate immune response of these MoDC to poly I:C (TLR 3 ligand), LPS (TLR 4 ligand), and CpG (TLR9 ligand) was tested. These TLR agonists did not stimulate induction of type I interferons by LPS or CpG but a strong response was observed to Poly I:C. This analysis shows that the generation of MoDCs in IL-13 yields cells of equivalent phenotype and function as IL-4 generated DC. However, for swine, in vitro generation of MoDC in IL-13 is likely to induce a more physiological cell population for study.