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Title:   Author  item
                                            KIM, SUNGWON - Virginia Techitem
                                            FOX, CHASITY - Virginia Techitem
                                            Jenkins, Markitem
                                            Fetterer, Raymonditem
                                            Miska, Kateitem
                                            DALLOUL, RAMI - Virginia Tech
  Submitted to: Developmental and Comparative Immunology
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 7/25/2014
                                    Publication  Date: 7/30/2014
                                    Citation: Kim, S., Fox, C., Jenkins, M.C., Fetterer, R.H., Miska, K.B., Dalloul, R. 2014. Both host and parasite MIF molecules bind to chicken macrophages via CD74 surface receptor. Developmental and Comparative Immunology. 47(2):319-326.Interpretive Summary: Studying immune responses of production animals such as the chicken is very important because during the period of growth (production) these animals often encounter pathogens that have to be cleared by the immune system of the host.  The research presented here concerns a molecule named Macrophage migration inhibitory factor (MIF) that affects movement of cells that are part of the immune system called macrophages.  It was shown that a molecule located on the surface of chicken macrophages named CD74 interacts with chicken MIF.  When MIF binds to the macrophage it will elicit a reaction from the cell such as inhibition of movement.  Additionally it was found that MIF present in a parasite of poultry called Eimeria, which infects the gut of the chicken causing anorexia, diarrhea and decreased weight gain, is also able to bind to CD74 on the surface of chicken macrophages.  Therefore the MIF of either avian or parasite origin is capable of binding the same molecule present on chicken macrophages.  This finding is significant because it demonstrates that a molecule present in a parasite that is pathogenic to chickens can be capable of modifying the immune system of the host.  It has been previously demonstrated that some parasites of humans and mice, are capable of modulating the immune response of the host in a manner that is favorable to the parasite and prevents its clearance by the host’s immune system.  In a past study our group reported that Eimeria MIF can inhibit the movement of chicken macrophages, and the current research documents for the first time that a component of the host’s immune system, the CD74 molecule on the surface of macrophages is affected by Eimeria MIF.  This research furthers the knowledge of the chicken immune response as well illustrating how a parasite that infects them can modulate its response.
                                Technical Abstract: Macrophage migration inhibitory factor (MIF) is recognized as a soluble factor that inhibits the random migration of macrophages and plays a pivotal immunoregulatory function in innate and adaptive immunity.  Our group has identified both chicken and Eimeria MIFs, and characterized their function in enhancing innate immune responses during inflammation.  In this study, we report that chicken CD74 (ChCD74), a type II transmembrane protein, functions as a macrophage surface receptor that binds to MIF molecules.  First, to examine the binding of MIF to chicken monocytes/macrophages, fresh isolated chicken peripheral blood mononuclear cells (PBMCs) were stimulated with rChIFN-' and then incubated with recombinant chicken MIF (rChMIF).  Immunofluorescence staining with anti-ChMIF followed by flow cytometry revealed the binding of MIF to stimulated PBMCs.  To verify that ChCD74 acts as a surface receptor for MIF molecule, full-length ChCD74p41 was cloned, expressed and its recombinant protein (rChCD74p41) transiently over-expressed with green fluorescent protein in chicken fibroblast DF-1 cells.  Fluorescence analysis revealed a higher population of cells double positive for CD74p41 and rChMIF, indicating the binding of rChMIF to DF-1 cells via rChCD74p41.  Using a similar approach, it was found that Eimeria MIF (EMIF), which is secreted by Eimeria sp. during infection, bound to chicken macrophages via ChCD74p41 as a surface receptor.  Together, this study provides conclusive evidence that both host and parasite MIF molecules bind to chicken macrophages via the surface receptor ChCD74.


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