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Title: Effects of avian triggering receptor expressed on myeloid cells (TREM-A1) activation on heterophil functional activites

item Kogut, Michael - Mike
item Genovese, Kenneth - Ken
item NERREN, JESSICA - Texas A&M University
item He, Louis

Submitted to: Developmental and Comparative Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/26/2011
Publication Date: 1/1/2012
Citation: Kogut, M.H., Genovese, K.J., Nerren, J., He, L.H. 2012. Effects of avian triggering receptor expressed on myeloid cells (TREM-A1) activation on heterophil functional activites. Developmental and Comparative Immunology. 36:157-165.

Interpretive Summary: White blood cells of the immune system in chickens must be able to “see” bacteria, like Salmonella, when they invade the body. One type of immune cell that we are studying in the chicken is called the heterophil. The heterophil is the first immune cell that bacteria come in contact with when it invades the body. The purpose of this research was to look for the way the heterophil sees Salmonella and then what happens when the heterophil sees the bacteria. We found that the heterophil has structures on its surface that are required to work together to see the bacteria. Once the bacteria are seen, the heterophil then produces a series of chemicals that calls other heterophils and immune cells to the site where the bacteria is invading. These cells can then prevent a serious infection. This research is important to vaccine manufacturers because it will help them make vaccines against Salmonella that will help the immune cells “see” the bacteria better and thus help the chicken get rid of the bacteria quicker.

Technical Abstract: A novel class of innate receptors called the triggering receptors expressed on myeloid cells (TREM) has been discovered and shown to be involved in innate inflammatory responses. The TREM family has been found in the chicken genome and consists of one activating gene (TREM-A1) and two inhibitory genes (TREM-B1 and TREM-B2). However, to date there have been no reports on the effects of activating the TREM molecules on the functional activity of the primary avian polymorphonuclear cell, the heterophil. To characterize the activation of avian heterophils, we evaluated the effect of receptor ligation on heterophil effector functions. A specific agonistic antibody (Ab) was generated against the peptide sequence of chicken TREM-A1 38-51aa (YNPRQQRWREKSWC). To study TREM-A1 mediated activation, purified peripheral blood heterophils were incubated with various concentrations of the anti-TREM-A1 Ab or control Ab against an irrelevant antigen. Activation via TREM-A1 induces a significant increase in phagocytosis of Salmonella enteritidis, a rapid degranulation, and a dramatic up-regulation in gene expression of the pro-inflammatory cytokine, IL-6, and the inflammatory chemokine, CXCLi2. However, we found no direct TREM-A1 stimulation of the heterophil oxidative burst. Like mammalian TREM, avian TREM-A1 ligation synergizes with the activation of Toll-like receptor-4 (TLR4) ligand, LPS. In addition, the synergistic activity of LPS and TREM-A1 resulted in a significant (p < 0.05) increased production of an oxidative burst. Taken together, these results suggest, unlike in mammalian neutrophils, TREM-A1 engagement activates a differential functional activation of avian heterophils but, like mammalian neutrophils, acts in synergy with TLR agonists. These results provide evidence of the function of TREM-A1 in heterophil biology and avian innate immunity.