Human cytomegalovirus impairs dendritic cell function: a novel mechanism of human cytomegalovirus immune escape

Beck, Kerstin; Meyer‐König, Ursula; Weidmann, Manfred; Nern, Christian; Hufert, Frank T.

doi:10.1002/eji.200323612

Cited by 73 publications

(106 citation statements)

References 36 publications

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“…This observation clearly suggests that a simple cellular receptor-mediated interaction with SARS-CoV is not by itself sufficient to activate DC. It has been reported that the ability to alter DC function by two large DNA viruses, HSV type 1 and human CMV, was mediated through soluble factors induced by immediate early and early gene products of viruses and was independent of a complete viral replication cycle (35,36). Whether certain SARS-CoV-encoded signals were required for the manipulation of DC function is currently under investigation.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Severe Acute Respiratory Syndrome and the Innate Immune Responses: Modulation of Effector Cell Function without Productive Infection

Tseng

Perrone

Zhu

et al. 2005

The Journal of Immunology

146

149

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Severe acute respiratory syndrome (SARS) caused by a novel human coronavirus (CoV), designated SARS-CoV, is a highly contagious respiratory disease with the lungs as a major target. Although the exact mechanism of SARS-CoV pathogenesis remains unknown, an intense, ill-regulated local inflammatory response has been suggested as partially responsible for the devastating lung pathology. We investigated the interaction of SARS-CoV with human macrophages (Mφ) and dendritic cells (DC), two key innate immune cells of the host immune system, by focusing on their susceptibility to viral infection and subsequent responses (e.g., phenotypic maturation, T cell-priming activity, phagocytosis, and cytokine production). We found neither cell to be permissive for SARS-CoV replication. However, incubation of Mφ and DC with live, but not gamma irradiation-inactivated, viruses appeared to better sustain their viability. Also, exposure to infectious SARS-CoV led to the phenotypic and functional maturation of DC, with regard to MHC class II and costimulatory molecule expression, T cell-stimulatory capacity, and cytokine production, respectively. Cytokine production was also observed for Mφ, which were refractory to cell surface phenotypic changes. Strikingly, live SARS-CoV could further prime cell types to respond to a suboptimal dose of bacterial LPS (100 ng/ml), resulting in massive release of IL-6 and IL-12. However, the endocytic capacity (e.g., Ag capture) of Mφ was significantly compromised upon exposure to infectious SARS-CoV. This study is the first demonstration that although SARS-CoV does not productively infect human Mφ or DC, it appears to exert differential effects on Mφ and DC maturation and functions, which might contribute to SARS pathogenesis.

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Section: Discussionmentioning

confidence: 99%

“…Importantly, the ability to alter the function of host cells by some viruses appears to be independent of viral replication (35,36). Therefore, we designed a series of experiments, as described below, aimed to determine whether SARS-CoV could have any impact on the function of M and DC.…”

Section: Sars-cov Does Not Add To the Cell Death Of Cultured M And Dcmentioning

confidence: 99%

Severe Acute Respiratory Syndrome and the Innate Immune Responses: Modulation of Effector Cell Function without Productive Infection

Tseng

Perrone

Zhu

et al. 2005

The Journal of Immunology

146

149

View full text Add to dashboard Cite

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“…In another study, a similar observation is reported in case of HCMV where signal delivery required for T cell activation is impaired in infected DCs which lead to persistent viral infection in the host system. In addition, HCMV infection diminishes the expression of adhesion molecules which in turn may lead to inefficient DC migration [11]. HCV induces immunosuppression in DCs during maturation.…”

Section: Dendritic Cell (Dc) Response During Viral Infectionmentioning

confidence: 99%

Immune Regulation and Evasion of Mammalian Host Cell Immunity During Viral Infection

et al. 2013

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The mammalian host immune system has wide array of defence mechanisms against viral infections. Depending on host immunity and the extent of viral persistence, either the host immune cells might clear/restrict the viral load and disease progression or the virus might evade host immunity by down regulating host immune effector response(s). Viral antigen processing and presentation in the host cells through major histocompatibility complex (MHC) elicit subsequent anti-viral effector T cell response(s). However, modulation of such response(s) might generate one of the important viral immune evasion strategies. Viral peptides are mostly generated by proteolytic cleavage in the cytosol of the infected host cells. CD8 ? T lymphocytes play critical role in the detection of viral infection by recognizing these peptides displayed at the plasma membrane by MHC-I molecules. The present review summarises the current knowledge on the regulation of mammalian host innate and adaptive immune components, which are operative in defence mechanisms against viral infections and the variety of strategies that viruses have evolved to escape host cell immunity. The understanding of viral immune evasion strategies is important for designing anti-viral immunotherapies.

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“…Since infected DCs could be paralysed [4] and made unable to ensure activation of In an in vitro model where HCMV-infected Wbroblasts were co-cultured with monocyte-derived dendritic cells, we demonstrated that immature DCs (iDC) acquired a mature phenotype (mDC), as assessed by an up-regulation of CD80, CD86 and CD83 expression on the cell surface and by the secretion of huge amounts of TNF- [24,25]. We further demonstrated that HCMV-infected Wbroblasts were sensitive to apoptosis mediated by TNF-, but only within the Wrst hours after addition of the virus.…”

Section: Role Of Cross-presentation To Bypass Viral Subversion and Inmentioning

confidence: 99%

“…Moreover, some viruses such as HIV and human cytomegalovirus (HCMV) use the C-type lectin receptor DC-SIGN on dendritic cells as a vector to ensure their transmission to other cells either in the periphery or in lymph nodes [1,2]. Direct arguments that DCs are real targets for HCMV in vivo are suggested, for instance, by the ability of the virus to infect hematopoietic progenitor cells [3] and by the presence of viral DNA in puriWed DCs from viremic renal transplant patients as well as from healthy virus carriers [4,5]. HCMV is a latent herpesvirus, which can be considered as a spearhead in exploiting co-existence with the host to develop numerous immunoevasion mechanisms, and virus-encoded immunoevasins have been described that impair many of dendritic cells functions including antigen presentation to CD4+ and CD8+ T cells [6].…”

Section: Introductionmentioning

confidence: 99%

Interplay between human cytomegalovirus and dendritic cells in T cell activation

Martin

Mandron

Davrinche

2008

Med Microbiol Immunol

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Control of human cytomegalovirus (HCMV) infection and prevention of associated diseases in immunocompetent hosts are ensured mainly by CD8+ T cells, in spite of numerous viral tricks to impair antigen presentation and activation of T cells. At sites of primary infection, dendritic cells (DCs) are in the forefront to ensure capture of viral antigens and their capacity to bypass the eVects of viral immunoevasins is crucial in moulding CD8+ T cell repertoire. In HCMV-seropositive donors, the spectrum of CD8+ T cells speciWcities was shown to include immediate-early (IE), early (E) and late (L) gene products, a surprising Wnding if we consider that expression of immunoevasins could paralyse infected DCs from the IE phase of infection. In the present report, we suggest that uninfected dendritic cells could acquire HCMV-antigens derived from input virus or neosynthesis, either in soluble forms or in association with infected dead cells resulting from death-ligand-mediated apoptosis and necrosis. Activation of naïve CD8+ T cells could then occur in lymph nodes through cross-presentation by antigen-loaded DCs, providing an explanation for shape and size of the memory compartment.

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Human cytomegalovirus impairs dendritic cell function: a novel mechanism of human cytomegalovirus immune escape

Cited by 73 publications

References 36 publications

Severe Acute Respiratory Syndrome and the Innate Immune Responses: Modulation of Effector Cell Function without Productive Infection

Severe Acute Respiratory Syndrome and the Innate Immune Responses: Modulation of Effector Cell Function without Productive Infection

Immune Regulation and Evasion of Mammalian Host Cell Immunity During Viral Infection

Interplay between human cytomegalovirus and dendritic cells in T cell activation

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