Accession Number : ADA450487


Title :   Activation of Triggering Receptor Expressed on Myeloid Cells-1 on Human Neutrophils by Marburg and Ebola Viruses


Descriptive Note : Journal article


Corporate Author : ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD


Personal Author(s) : Mohamadzadeh, Mansour ; Coberley, Sadie S. ; Olinger, Gene G. ; Kalina, Warren V. ; Ruthel, Gordon ; Fullter, Claudette L. ; Swenson, Dana L. ; Pratt, William D. ; Kuhns, Douglas B. ; Schmaljohn, Alan L.


Full Text : http://www.dtic.mil/get-tr-doc/pdf?AD=ADA450487


Report Date : 21 APR 2006


Pagination or Media Count : 11


Abstract : Marburg virus (MARV) and Ebola virus (EBOV), members of the viral family Filoviridae, cause fatal hemorrhagic fevers in humans and nonhuman primates. High viral burden is coincident with inadequate adaptive immune responses and robust inflammatory responses, and virus-mediated dysregulation of early host defenses has been proposed. Recently, a novel class of innate receptors called the triggering receptors expressed in myeloid cells (TREM) has been discovered and shown to play an important role in innate inflammatory responses and sepsis. Here, we report that MARV and EBOV activate TREM-1 on human neutrophils, resulting in DAP12 phosphorylation, TREM-1 shedding, mobilization of intracellular calcium, secretion of proinflammatory cytokines, and phenotypic changes. A peptide specific to TREM-1 diminished the release of tumor necrosis factor alpha by filovirus-activated human neutrophils in vitro, and a soluble recombinant TREM-1 competitively inhibited the loss of cell surface TREM-1 that otherwise occurred on neutrophils exposed to filoviruses. These data imply direct activation of TREM-1 by filoviruses and also indicate that neutrophils may play a prominent role in the immune and inflammatory responses to filovirus infections.


Descriptors :   *EXPOSURE(GENERAL) , *NEOPLASMS , *HEMORRHAGIC FEVERS , *INFECTIOUS DISEASES , *VIRUSES , *VIROLOGY , *EBOLA VIRUS , *CELLS(BIOLOGY) , CALCIUM , ACTIVATION , ADAPTIVE SYSTEMS , IMMUNITY , MANEUVERABLE REENTRY VEHICLES , ARBOVIRUSES , POLYMORPHONUCLEAR NEUTROPHILS , SEPSIS , NECROSIS , RECEPTOR SITES(PHYSIOLOGY) , SENSE ORGANS , BONE MARROW , INFLAMMATION , CYTOKINES , PRIMATES , RESPONSE(BIOLOGY) , EXPOSURE(PHYSIOLOGY) , ANIMALS , HUMANS , MOBILIZATION , DEFENSE SYSTEMS


Subject Categories : ANATOMY AND PHYSIOLOGY
      MICROBIOLOGY
      MEDICINE AND MEDICAL RESEARCH


Distribution Statement : APPROVED FOR PUBLIC RELEASE