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

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

doi:10.1128/jvi.00543-06

Cited by 93 publications

(102 citation statements)

References 46 publications

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“…Conversely, the binding of filoviruses to C-type lectin molecules is significantly inhibited by the carbohydrate mannan, which indicates that the binding is due to the interaction between carbohydrate motifs on the surface of host cells and N-linked carbohydrate structures of glycoprotein on the filoviral surface. Recently, we also observed that a class of immunorecognition receptors known as TREMs, which are implicated in the amplification of septic shock and cell activation, might have a crucial early role in the interaction of filoviruses with neutrophils 12 , monocytes and mature DCs.…”

Section: Invariant Natural Killer T Cellmentioning

confidence: 98%

“…Viral particles, in turn, are able to trigger polymorphonuclear leukocytes (such as neutrophils) to expel the contents of their preformed granules and enter a state of activation 12 . Such early inflammatory responses are not extraordinary and might even be helpful in shaping normal immune responses 30 , but might also exacerbate an underlying early immune response dysfunction that originates principally in DCs.…”

Section: Box 1 | Filovirus-disease Basicsmentioning

confidence: 99%

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How Ebola and Marburg viruses battle the immune system

2007

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PantropicTending towards the capacity to infect a wide range of cells and organs. CoagulopathyRefers to a group of conditions of the blood-clotting system in which bleeding is prolonged and excessive. Cell tropismA virus's affinity for or tendency towards preferential infection of certain cells. How Ebola and Marburg viruses battle the immune systemMansour Mohamadzadeh* ‡ , Lieping Chen ‡ , and Alan L. Schmaljohn* Abstract | The filoviruses Ebola and Marburg have emerged in the past decade from relative obscurity to serve now as archetypes for some of the more intriguing and daunting challenges posed by such agents. Public imagination is captured by deadly outbreaks of these viruses and reinforced by the specter of bioterrorism. As research on these agents has accelerated, it has been found increasingly that filoviruses use a combination of familiar and apparently new ways to baffle and battle the immune system. Filoviruses have provided thereby a new lens through which to examine the immune system itself. R E V I E W S Report Documentation PageForm Public reporting burden for the collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden, to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to a penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number.

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Section: Invariant Natural Killer T Cellmentioning

confidence: 98%

Section: Box 1 | Filovirus-disease Basicsmentioning

confidence: 99%

How Ebola and Marburg viruses battle the immune system

2007

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“…1 TREM-1 expression is further up-regulated by TLR ligands. Binding of TREM-1 to endogenous ligand(s) expressed on granulocytes and platelets and present in sera of septic patients, [2][3][4] as well as to exogenous ligands on Marburg and Ebola viruses, 5 has been described. The exact nature of TREM-1 ligand(s), however, remains elusive.…”

Section: Introductionmentioning

confidence: 99%

Btk is a positive regulator in the TREM-1/DAP12 signaling pathway

Ormsby

Schlecker

Ferdin

et al. 2011

Blood

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IntroductionTREM-1 belongs to the immunoglobulin (Ig)-like superfamily of receptors. In humans, TREM-1 is expressed on neutrophils and CD14 high monocytes. 1 TREM-1 expression is further up-regulated by TLR ligands. Binding of TREM-1 to endogenous ligand(s) expressed on granulocytes and platelets and present in sera of septic patients, 2-4 as well as to exogenous ligands on Marburg and Ebola viruses, 5 has been described. The exact nature of TREM-1 ligand(s), however, remains elusive. Engagement of TREM-1 by agonistic monoclonal antibodies (mAbs) results in respiratory burst, degranulation, phagocytosis, secretion of pro-inflammatory cytokines such as TNF-␣, of the chemokines, IL-8 and monocyte chemotactic protein-1 (MCP-1), and in the up-regulation of cell surface expressed differentiation/activation markers. 1 In animal models of lipopolysacharide (LPS)-induced septic shock and microbial sepsis caused by live Escherichia coli, application of a soluble TREM-1-Ig fusion protein greatly increased survival of experimental animals indicating the importance of TREM-1 in the amplification of inflammation. 6 TREM-1 possesses a short intracellular part that lacks intrinsic signaling motifs. Instead, it is coupled to the immunoreceptor tyrosine-based activation motif (ITAM)-containing adaptor protein, DAP12. 1 TREM-1 engagement leads to Ca 2ϩ mobilization and phosphorylation of several proteins including DAP12, extracellular-signal regulated kinase (Erk1/2), phospholipase C␥ (PLC␥) 1 and the adaptor protein NTAL that further interacts with Grb2. 7 Recently, it was reported that the adaptor protein CARD9 is essential for TREM-1-induced secretion of TNF-␣, IL-2 and IL-12p40 by mouse bone marrow-derived dendritic cells (BMDCs). 8 Bruton tyrosine kinase (Btk), a member of the Tec family of protein tyrosine kinases (PTKs), is involved in signaling via a variety of receptors including the B-cell receptor (BCR), cytokine receptors and integrins. 9,10 Loss of Btk function causes X-linked agammaglobulinemia (XLA), a rare primary immunodeficiency disease. 11,12 Mutations causing XLA have been described in all Btk domains as well as in noncoding sequences of the gene. 13 XLA is manifested by severe defects in early B-cell development, resulting in an almost complete absence of peripheral B cells and Igs of all classes. Affected individuals suffer from recurrent bacterial and enteroviral infections. 9 In mice, the R28C point mutation in the pleckstrin homology (PH) domain of Btk leads to X-linked immunodeficiency (Xid). 14 In innate immune cells, the role of Btk is less clear. Btk has been implicated in several pathways in myeloid cells. 10 Btk associates with certain TLRs and their downstream signaling molecules. 15 Contradictory results were obtained from studies of TLR stimulation of monocytes of XLA patients. In one report, relative to healthy controls, monocytes of XLA patients secreted reduced amounts of TNF-␣ upon LPS stimulation. 16 On the other hand, Perez et al 17 described that monocytes of XLA patients showed similar TN...

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“…These included genes that regulate intercellular communication between DC and NK cells, TREM1 signaling, and DC maturation (Table 3). Within the TREM1 pathway, molecules that mediate pathogen recognition and subsequent inflammation (TREM1, NOD2, and TYROBP) (2,22,26) and chemoattractant molecules (MIP-1␣, MCP-1, and MCP-3) had the highest expression in IL1RKO mice among all mouse strains (Fig. 6A).…”

Section: Resultsmentioning

confidence: 99%

“…Previous reports have shown that TREM1 amplifies inflammation during bacterial (2) and Ebola virus (22) infections in part through the activation of DAP12 signaling pathways and is linked to increased proinflammatory cytokine secretion and survival of neutrophils and monocytes. Our findings related to the TREM1 pathway at 1 dpi are particularly interesting, given the link between this molecule and the host response to other microbial pathogens.…”

Section: Discussionmentioning

confidence: 99%

Genomic Profiling of Tumor Necrosis Factor Alpha (TNF-α) Receptor and Interleukin-1 Receptor Knockout Mice Reveals a Link between TNF-α Signaling and Increased Severity of 1918 Pandemic Influenza Virus Infection

Belisle

Tisoncik

Korth

et al. 2010

J Virol

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The influenza pandemic of 1918 to 1919 was one of the worst global pandemics in recent history. The highly pathogenic nature of the 1918 virus is thought to be mediated in part by a dysregulation of the host response, including an exacerbated proinflammatory cytokine response. In the present study, we compared the host transcriptional response to infection with the reconstructed 1918 virus in wild-type, tumor necrosis factor (TNF) receptor-1 knockout (TNFRKO), and interleukin-1 (IL-1) receptor-1 knockout (IL1RKO) mice as a means of further understanding the role of proinflammatory cytokine signaling during the acute response to infection. Despite reported redundancy in the functions of IL-1␤ and TNF-␣, we observed that reducing the signaling capacity of each of these molecules by genetic disruption of their key receptor genes had very different effects on the host response to infection. In TNFRKO mice, we found delayed or decreased expression of genes associated with antiviral and innate immune signaling, complement, coagulation, and negative acute-phase response. In contrast, in IL1RKO mice numerous genes were differentially expressed at 1 day postinoculation, including an increase in the expression of genes that contribute to dendritic and natural killer cell processes and cellular movement, and gene expression profiles remained relatively constant at later time points. We also observed a compensatory increase in TNF-␣ expression in virus-infected IL1RKO mice. Our data suggest that signaling through the IL-1 receptor is protective, whereas signaling through the TNF-␣ receptor increases the severity of 1918 virus infection. These findings suggest that manipulation of these pathways may have therapeutic benefit.

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

Abstract: Marburg virus (MARV) and Ebola virus (EBOV), members of the viral family

Cited by 93 publications

References 46 publications

How Ebola and Marburg viruses battle the immune system

How Ebola and Marburg viruses battle the immune system

Btk is a positive regulator in the TREM-1/DAP12 signaling pathway

Genomic Profiling of Tumor Necrosis Factor Alpha (TNF-α) Receptor and Interleukin-1 Receptor Knockout Mice Reveals a Link between TNF-α Signaling and Increased Severity of 1918 Pandemic Influenza Virus Infection

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