Journal of Virology, July 2006, p. 7235-7244, Vol. 80, No. 14
0022-538X/06/$08.00+0 doi:10.1128/JVI.00543-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
Activation of Triggering Receptor Expressed on Myeloid Cells-1 on Human Neutrophils by Marburg and Ebola Viruses
Mansour Mohamadzadeh,1*
Sadie S. Coberley,1
Gene G. Olinger,1
Warren V. Kalina,1
Gordon Ruthel,1
Claudette L. Fuller,1
Dana L. Swenson,1
William D. Pratt,1
Douglas B. Kuhns,2 and
Alan L. Schmaljohn1
U.S. Army Medical Research Institute for Infectious Diseases, Frederick, Maryland,1
National Cancer Institute, Frederick, Maryland2
Received 15 March 2006/
Accepted 21 April 2006
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.
* Corresponding author. Mailing address: USAMRIID, 1425 Porter Street, Frederick, MD 21702. Phone: (301) 619-8484. Fax: (301) 619-2290. E-mail: Mansour.Mohamadzadeh{at}amedd.army.mil.
Journal of Virology, July 2006, p. 7235-7244, Vol. 80, No. 14
0022-538X/06/$08.00+0 doi:10.1128/JVI.00543-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
This article has been cited by other articles:
-
Ho, C.-C., Liao, W.-Y., Wang, C.-Y., Lu, Y.-H., Huang, H.-Y., Chen, H.-Y., Chan, W.-K., Chen, H.-W., Yang, P.-C.
(2008). TREM-1 Expression in Tumor-associated Macrophages and Clinical Outcome in Lung Cancer. Am. J. Respir. Crit. Care Med.
177: 763-770
[Abstract]
[Full Text]
-
Dower, K., Ellis, D. K., Saraf, K., Jelinsky, S. A., Lin, L.-L.
(2008). Innate Immune Responses to TREM-1 Activation: Overlap, Divergence, and Positive and Negative Cross-Talk with Bacterial Lipopolysaccharide. J. Immunol.
180: 3520-3534
[Abstract]
[Full Text]
-
Klesney-Tait, J., Colonna, M.
(2007). Uncovering the TREM-1-TLR connection. Am. J. Physiol. Lung Cell. Mol. Physiol.
293: L1374-L1376
[Full Text]
-
Gomez-Pina, V., Soares-Schanoski, A., Rodriguez-Rojas, A., del Fresno, C., Garcia, F., Vallejo-Cremades, M. T., Fernandez-Ruiz, I., Arnalich, F., Fuentes-Prior, P., Lopez-Collazo, E.
(2007). Metalloproteinases Shed TREM-1 Ectodomain from Lipopolysaccharide-Stimulated Human Monocytes. J. Immunol.
179: 4065-4073
[Abstract]
[Full Text]
-
Haselmayer, P., Grosse-Hovest, L., von Landenberg, P., Schild, H., Radsak, M. P.
(2007). TREM-1 ligand expression on platelets enhances neutrophil activation. Blood
110: 1029-1035
[Abstract]
[Full Text]
Copyright © 2006 by the American Society for Microbiology. All rights reserved.