Suppression of Proinflammatory Cytokine Expression by Herpes Simplex Virus Type 1

Mogensen, Trine H.; Melchjorsen, Jesper; Malmgaard, Lene; Casola, Antonella; Paludan, Søren R.

doi:10.1128/jvi.78.11.5883-5890.2004

Cited by 67 publications

(68 citation statements)

References 50 publications

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“…Furthermore, it has been reported that a biphasic production of cytokines takes place in some infected cell types, one that is dependent upon virus replication and one that is not (24). To examine this possibility, we studied cytokine expression profiles in TLR2 Ϫ/Ϫ microglia by microarray at 16 h p.i., in addition to 5 h p.i., and no significant difference was observed between the two time points (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Cutting Edge: TLR2-Mediated Proinflammatory Cytokine and Chemokine Production by Microglial Cells in Response to Herpes Simplex Virus

Aravalli

Rowen

et al. 2005

The Journal of Immunology

211

172

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Recent studies indicate that TLRs are critical in generating innate immune responses during infection with HSV-1. In this study, we investigated the role of TLR2 signaling in regulating the production of neuroimmune mediators by examining cytokine and chemokine expression using primary microglial cells obtained from TLR2−/− as well as wild-type mice. Data presented here demonstrate that TLR2 signaling is required for the production of proinflammatory cytokines and chemokines: TNF-α, IL-1β, IL-6, IL-12, CCL7, CCL8, CCL9, CXCL1, CXCL2, CXCL4, and CXCL5. CXCL9 and CXCL10 were also induced by HSV, but their production was not dependent upon TLR2 signaling. Because TLR2−/− mice display significantly reduced mortality and diminished neuroinflammation in response to brain infection with HSV, the TLR2-dependent cytokines identified here might function as key players influencing viral neuropathogenesis.

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Section: Discussionmentioning

confidence: 99%

Cutting Edge: TLR2-Mediated Proinflammatory Cytokine and Chemokine Production by Microglial Cells in Response to Herpes Simplex Virus

Aravalli

Rowen

et al. 2005

The Journal of Immunology

211

172

View full text Add to dashboard Cite

show abstract

“…For instance, vesicular stomatitis virus M protein inhibits nuclear-to-cytoplasmic export of mRNAs, including those encoding IFN-␣/␤ (124). Moreover, in studies of virus-host interactions, HSV-1 has been reported to suppress proinflammatory cytokine production by a mechanism involving destabilization of mRNA encoding proinflammatory cytokines, in a process dependent on the viral immediate-early proteins ICP4 and ICP27, thus impeding the antiviral host response to infection (260).…”

Section: Viral Immune Evasion Strategiesmentioning

confidence: 99%

Pathogen Recognition and Inflammatory Signaling in Innate Immune Defenses

2009

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SUMMARY The innate immune system constitutes the first line of defense against invading microbial pathogens and relies on a large family of pattern recognition receptors (PRRs), which detect distinct evolutionarily conserved structures on pathogens, termed pathogen-associated molecular patterns (PAMPs). Among the PRRs, the Toll-like receptors have been studied most extensively. Upon PAMP engagement, PRRs trigger intracellular signaling cascades ultimately culminating in the expression of a variety of proinflammatory molecules, which together orchestrate the early host response to infection, and also is a prerequisite for the subsequent activation and shaping of adaptive immunity. In order to avoid immunopathology, this system is tightly regulated by a number of endogenous molecules that limit the magnitude and duration of the inflammatory response. Moreover, pathogenic microbes have developed sophisticated molecular strategies to subvert host defenses by interfering with molecules involved in inflammatory signaling. This review presents current knowledge on pathogen recognition through different families of PRRs and the increasingly complex signaling pathways responsible for activation of an inflammatory and antimicrobial response. Moreover, medical implications are discussed, including the role of PRRs in primary immunodeficiencies and in the pathogenesis of infectious and autoimmune diseases, as well as the possibilities for translation into clinical and therapeutic applications.

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“…For instance, viruses can inhibit interferon and cytokine production (40,55) and function (4,44,57) and can also utilize activated NF-B to kick-start viral early (E) gene expression programs (5,31,42,49,52). Furthermore, inflammatory cells that are attracted to the sites of infection as a consequence of pathway activation and chemokine production can be hijacked by viruses to support viral spread (27).…”

mentioning

confidence: 99%

Human Cytomegalovirus Blocks Tumor Necrosis Factor Alpha- and Interleukin-1β-Mediated NF-κB Signaling

Montag

Wagner

Gruska

et al. 2006

J Virol

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NF-B plays an important role in the early cellular response to pathogens by activating genes involved in inflammation, immune response, and cell proliferation and survival. NF-B is also utilized by many viral pathogens, like human cytomegalovirus (HCMV), to activate their own gene expression programs, reflecting intricate roles for NF-B in both antiviral defense mechanisms and viral physiology. Here we show that the NF-B signaling pathway stimulated by proinflammatory cytokines tumor necrosis factor alpha (TNF-␣) and interleukin-1␤ (IL-1␤) becomes inhibited in HCMV-infected cells. The block to NF-B signaling is first noticeable during the early phase of infection but is fully established only at later times. Biochemical and genetic evidence demonstrates that the viral inhibition of proinflammatory signaling by distinct cytokines occurs upstream of the convergence point of NF-B-activating pathways, i.e., the IB kinase complex, and that it is mediated via different mechanisms. Consistent with this, we further show that an HCMV variant that has lost the ability to downregulate TNF-␣-induced NF-B signaling also fails to downregulate surface expression of TNF receptor 1, thereby mechanistically linking the inhibition of TNF-␣-induced NF-B signaling by HCMV to TNF receptor targeting. Our data support a model whereby HCMV inhibits cytokine-induced NF-B signaling at later times during infection, and we suggest that this contributes to the inhibition of the cell's antiviral defense program.

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Suppression of Proinflammatory Cytokine Expression by Herpes Simplex Virus Type 1

Cited by 67 publications

References 50 publications

Cutting Edge: TLR2-Mediated Proinflammatory Cytokine and Chemokine Production by Microglial Cells in Response to Herpes Simplex Virus

Cutting Edge: TLR2-Mediated Proinflammatory Cytokine and Chemokine Production by Microglial Cells in Response to Herpes Simplex Virus

Pathogen Recognition and Inflammatory Signaling in Innate Immune Defenses

Human Cytomegalovirus Blocks Tumor Necrosis Factor Alpha- and Interleukin-1β-Mediated NF-κB Signaling

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