Activation of triggering receptor expressed on myeloid cells-1 on human neutrophils by Marburg and Ebola viruses

Mansour Mohamadzadeh, Sadie S. Coberley, Gene G. Olinger, Warren V. Kalina, Gordon Ruthel, Claudette L. Fuller, Dana L. Swenson, William D. Pratt, Douglas B. Kuhns, Alan L. Schmaljohn

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)7235-7244
Number of pages10
JournalJournal of virology
Volume80
Issue number14
DOIs
StatePublished - Jul 2006
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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