TREM-2 Promotes The Survival Of Brucella Abortus Via Depressing Macrophage Activation

Brucella is the cause of Brucellosis, which is a zoonotic disease transmitted among the world. In comparison to other intracellular bacterial, Brucella organisms are devoid of fimbria, capsules and plasmids, which are the classic effectors involved in virulence. Additionally, Brucella PAMPs, including Br-LPS, lipoproteins, and flagellin, are poor inducers of innate immunity responses, endowing Brucella with the ability to flee from the capture of macrophages(M?s), dendritic cells(DCs) along with no significant changes or damages to host cells. Once escaping from the immune system, Brucella is allowed to replicate and remain its virulence. Therefore, these findings underline the importance of macrophage activation in regulating the survival of Brucella.Triggering receptor expressed on myeloid cells-2(TREM-2) is a cell surface receptor primarily expressed on macrophages and dendritic cells. TREM-2 functions as a phagocytic receptor for bacteria as well as an inhibitor of Toll like receptors(TLR) induced inflammatory cytokines, which can induce the activation of macrophages. However, the role of TREM-2 in Brucella intracellular growth remains unknown.To investigate whether TREM-2 is involved in Brucella intracellular survival, we chose bone marrow derived macrophages(BMDMs), in which TREM-2 is stably expressed, as cell model. Colony formation Units(CFUs) assay suggests that TREM-2 is involved in the internalization of Brucella abortus(B. abortus) by macrophages, while silencing of TREM-2 decreases intracellular survival of B.abortus. To further study the underlying mechanisms of TREM-2-mediated bacterial intracellular survival, we examined the activation of B. abortus-infected macrophages through determining the kinetics of activation of the three MAPKs, including ERK, JNK and p38, and measuring TNF production in response to lipopolysaccharide(LPS) of Brucella(Br LPS) or B. abortus stimulation. Our data show that TREM-2 deficiency promotes activation of Brucella-infected macrophages. Moreover, our data also demonstrate that macrophage activation promotes killing of Brucella by enhancing nitric oxygen(NO), but not reactive oxygen species(ROS) production, macrophage apoptosis or cellular death. Taken together, these findings provide a novel interpretation of Brucella intracellular growth through inhibition of NO production produced by TREM-2-mediated activated macrophages.