Expression of TREM-1 is triggered by flaviviruses: possible role in virus-associated innate immune responses (P1381)

Abstract

Abstract Activation of Triggering Receptor Expressed on Myeloid cells 1 (TREM-1), an immunoreceptor expressed mainly on immune cells results in a cascade of inflammatory effects including cytokine production. In addition, TREM-1 also modulates signaling cascades of other PRRs such as TLRs and NLRs. Engagement of the TREM-1 receptor via adaptor protein DAP12 leads to the activation of downstream kinases, mobilization of intracellular calcium and production of pro-inflammatory cytokines. Innate immune responses are essential for the clearance, dissemination and neurovirulence of West Nile virus (WNV), a neurotropic flavivirus, which has emerged in the U.S. as a significant cause of viral encephalitis in humans. However, the role of TREM-1 signaling pathway in immunity to flaviviruses is unclear. In this study we investigated the changes in the expression kinetics and activation of TREM-1 following WNV infection. Expression of TREM-1 was markedly increased in WNV-infected mouse immune cells and embryonic fibroblasts (MEFs) at 48 hrs after infection and in the mouse brain at day 8 after infection. Further, activation of TREM-1 using agonist antibody resulted in an increase in the levels of IFN-β and key cytokines in WNV-infected MEFs. Our results so far indicate a possible role of TREM-1 in the induction of inflammatory innate immune responses to WNV and further studies are ongoing to characterize unexplored mechanisms of TREM-1 associated with the pathogenesis of flaviviruses.