Nespecifična imunost na hantaviruse
|2013-11||4393||HANTA-INNATE||01.07.2014 - 30.11.2018||Završio||995.000,00 Kn|
Biomedicina i zdravstvoZnanstvena polja:
Temeljne medicinske znanostiUstanova:
Ništa od navedenogSuradnici:
Ofer Mandelboim, Lidija Cvetko Krajinović, Ivan-Christian Kurolt, Ante Tadin, OKTAVIJA ĐAKOVIĆ RODE, Dragan Ledina, ĐURĐICA CEKINOVIĆ, Ljiljana Žmak, Petra SvobodaKljučne riječi:
hantavirses, Puumala, Dobrava, reoinfection, acute infection, monovytes, macrophages, NK cells, innate immunity, hemorrhagic fever with renal syndromeSažetak:
Hantaviruses (HTV), family Bunyaviridae, are emerging, enveloped RNA viruses, which cause hemorrhagic fever with renal syndrome (HFRS) in Croatia and in the rest of Europe, where two main HTV cause HFRS: Puumala (PUUV) and Dobrava (DOBV). A broad spectrum of HFRS clinical conditions has been recognized, ranging from inapparent or mild to a fulminant hemorrhagic process with severe renal failure and death. The strong proinflammatory response during acute infection in humans is probably responsible for viral clearance but also for potentially fatal proinflammatory-mediated disease. Innate immunity is the first line of defense to various pathogens which may substantially determine the further development and outcome of disease. There is strong lack of knowledge on innate immune response to HTV in acute phase of disease and no evidence on immune response to reinfection with HTV at all. Overall objective of this project is to identify some key elements of innate immune response in acute HFRS infection and in experimentally simulated HTV reinfection at the level of monocytes/macrophages, NK cells, their crosstalk, “memory” and potential mediation by microRNAs (miRNAs). For that purpose, ex vivo experiments on peripheral blood mononuclear cells, monocytes/macrophages and NK cells will be performed in patients with acute HFRS and patients previously encountered HFRS. Primary monocytes/macrophages and NK cells will be additionally infected with HTV and co-cultivated. In order to asses potential miRNAs role, some inhibition experiments will be performed. Computational analysis will follow all experimental process in order to generate new data, pursue study in right direction and indicate important signaling pathways for the future research. Such concept may represent the next step in the design of future vaccines for HTV.