Impaired Lymphoid Chemokine-Mediated Migration due to a Block on the Chemokine Receptor Switch in Human Cytomegalovirus-Infected Dendritic Cells

Moutaftsi, Magdalena; Brennan, Paul; Spector, Stephen A.; Tabi, Zsuzsanna

doi:10.1128/jvi.78.6.3046-3054.2004

Cited by 55 publications

(58 citation statements)

References 36 publications

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“…Interestingly, when we investigated the expression profiles of CXCR4 and CCR7 in HSV-1-infected mature DCs by Affymetrix gene-chip analyses and RT-PCR time-course experiments, we found a dramatic downregulation of these molecules that, in consequence, led to a reduced surface expression of these two molecules. A similar observation was made by Moutaftsi et al (2004) with HCMV-infected DCs. Salio et al (1999) reported that immature DCs infected with disabled infectious singlecycle (DISC) HSV-1 encoding GFP failed to respond to Epstein-Barr virus-induced molecule 1 ligand chemokine (ELC, another name for CCL19), whereas mature DCs did respond.…”

Section: Discussionsupporting

confidence: 56%

Infection of mature dendritic cells with herpes simplex virus type 1 dramatically reduces lymphoid chemokine-mediated migration

Prechtel

Turza

Kobelt

et al. 2005

Journal of General Virology

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Herpes simplex virus type 1 (HSV-1) is able to establish latency in infected individuals. In order to characterize potential new immune-escape mechanisms, mature dendritic cells (DCs) were infected with HSV-1 and total cellular RNA was isolated from infected and mock-infected populations at different time points. RNA profiling on Affymetrix Human Genome U133A arrays demonstrated a dramatic downregulation of the migration-mediating surface molecules CCR7 and CXCR4, an observation that was further confirmed by RT-PCR and fluorescence-activated cell sorting analyses. Furthermore, migration assays revealed that, upon infection of mature DCs, CCR7-and CXCR4-mediated migration towards the corresponding CCL19 and CXCL12 chemokine gradients was strongly reduced. It is noteworthy that the infection of immature DCs with HSV-1 prior to maturation led to a failure of CCR7 and CXCR4 upregulation during DC maturation and, as a consequence, also induced a block in their migratory capacity. Additional migration assays with a Dvhs mutant virus lacking the virion host shutoff (vhs) gene, which is known to degrade cellular mRNAs, suggested a vhs-independent mechanism. These results indicate that HSV-1-infected mature DCs are limited in their capacity to migrate to secondary lymphoid organs, the areas of antigen presentation and T-cell stimulation, thus inhibiting an antiviral immune response. This represents a novel, previously unrecognized mechanism for HSV-1 to escape the human immune system. INTRODUCTIONDendritic cells (DCs) are bone marrow-derived leukocytes and represent the best-known group of antigen-presenting cells (APCs) today. In order to induce specific T cellmediated immune responses, they act as the sentinels of the immune system and lie in wait in an immature state in almost all peripheral tissues (Banchereau & Steinman, 1998). Maturation is induced by contact of immature DCs with various products of infectious agents (Aliprantis et al., 1999;Brightbill et al., 1999;Cella et al., 1999). During maturation, DCs lose their ability to take up antigens and migrate from the sites of antigen accumulation to the areas of antigen presentation, primarily the T-cell zones of the secondary lymphoid organs (Banchereau & Steinman, 1998;Ridge et al., 1998).Immature DCs differ significantly from mature DCs in their response to specific chemokines, their ability to migrate and their capacity to stimulate immune responses (Gunn, 2003). Whilst immature DCs respond to many CC and CXC chemokines, such as CCL3 (MIP-1a), CCL4 (MIP-1b), CCL5 (RANTES) and CCL20 (MIP-3a), the expression or activity of the corresponding receptors is reduced or abolished completely in mature DCs 1998). As a consequence of the enhanced expression of CCR7 and CXCR4, mature DCs show an increased response to CCL19 (MIP-3b) and CXCL12 (SDF-1a) (Cavanagh & Von Andrian, 2002; Delgado et al., 1998; Förster et al., 1999;Gunn et al., 1999). The necessity of CCR7 expression for the induction of a primary immune response (Förster et al., 1999;Parlato et al., 2001) has ...

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Section: Discussionsupporting

confidence: 56%

Infection of mature dendritic cells with herpes simplex virus type 1 dramatically reduces lymphoid chemokine-mediated migration

Prechtel

Turza

Kobelt

et al. 2005

Journal of General Virology

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“…Moutaftsi and colleagues 31 recently demonstrated impaired lymphoid chemokine-mediated migration of HCVM-infected DC, and Varani et al 11 observed reduced migration of HCMVinfected immature DC in response to inflammatory chemokines. Thus, inhibition of DC migration by HCMV has been proposed as a potential viral strategy to paralyze the host's immune response.…”

Section: Discussionmentioning

confidence: 99%

Hepatitis C virus E2 and CD81 interaction may be associated with altered trafficking of dendritic cells in chronic hepatitis C†

et al. 2006

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“…It is therefore not surprising that viruses other than MV (including HSV-1, HCMV and vaccinia virus) also failed to upregulate CCR7 on infected DCs (Humrich et al, 2007;Moutaftsi et al, 2004;Prechtel et al, 2005), though this is not understood on a mechanistic basis. As CCR7 is regulated by NF-kB, AP-1 and also MAPK (Ardeshna et al, 2002;Hopken et al, 2002;Mathas et al, 2002), induction of CCR7 can be dissociated from that of most other maturation markers in both DCs and Langerhans cells (Geissmann et al, 2002;Hegde et al, 2004).…”

Section: Hallmarks Of Measles Virus (Mv)-induced Immuno-mentioning

confidence: 99%

“…DC chemotaxis is targeted during immune evasion by vaccinia virus, human cytomegalovirus (HCMV), herpes simplex virus (HSV) and influenza A virus (Humrich et al, 2007;Moutaftsi et al, 2004;Prechtel et al, 2005;Salentin et al, 2003;Varani et al, 2005), but it is not known whether MV modulates these properties too.…”

Section: Hallmarks Of Measles Virus (Mv)-induced Immuno-mentioning

confidence: 99%

Measles virus modulates chemokine release and chemotactic responses of dendritic cells

Abt

Gassert

Schneider‐Schaulies

2009

Journal of General Virology

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Interference with dendritic cell (DC) maturation and function is considered to be central to measles virus (MV)-induced immunosuppression. Temporally ordered production of chemokines and switches in chemokine receptor expression are essential for pathogen-driven DC maturation as they are prerequisites for chemotaxis and T cell recruitment. We found that MV infection of immature monocyte-derived DCs induced transcripts specific for CCL-1, -2, -3, -5, -17 and -22, CXCL-10 and CXCL-11, yet did not induce and CCL-20 at the mRNA and protein level. Within 24 h post-infection, T cell attraction was not detectably impaired by these cells. MV infection failed to promote the switch from CCR5 to CCR7 expression and this correlated with chemotactic responses of MV-matured DC cultures to CCL-3 rather than to CCL-19. Moreover, the chemotaxis of MV-infected DCs to either chemokine was compromised, indicating that MV also interferes with this property independently of chemokine receptor modulation. Hallmarks of measles virus (MV)-induced immuno-suppression include lymphopenia and proliferative unresponsiveness of peripheral blood lymphocytes to mitogens (Griffin et al., 1994;Schneider-Schaulies & ter Meulen, 2002). The ability of myeloid dendritic cells (DCs) to both initiate T cell activation and mediate viral transport to secondary lymphatics has determined that they are central to MV-specific immunity and immunosuppression (Pollara et al., 2005;Steinman et al., 2003). MV targets CD150 + haematopoetic cells (Condack et al., 2007; de Swart et al., 2007), and in experimentally infected macaques, mucosal DCs replicate MV in vivo (de Swart et al., 2007). DCs are generated from precursors and they mature upon MV exposure in vitro (Dubois et al., 2001;Fugier-Vivier et al., 1997;Grosjean et al., 1997;Kaiserlian et al., 1997;Schnorr et al., 1997;Servet-Delprat et al., 2000), this involves toll-like receptor (TLR) signalling and type I interferon (IFN) (Minagawa et al., 2001;Schnorr et al., 1997;Servet-Delprat et al., 2000;Shingai et al., 2007). MV-matured DCs (MV-DCs) fail to promote allogenic T cell expansion, which results from signalling by the viral glycoproteins expressed on the DC surface to T cells (Kerdiles et al., 2006;Schneider-Schaulies & Dittmer, 2006;Schneider-Schaulies et al., 2003;Servet-Delprat et al., 2003).Maturing DCs change their responsiveness from initially pro-inflammatory to lymphoid-type chemokines (reflected by a switch from CCR5 to CCR7 surface expression) which allows egress from peripheral sites where they respond to CCR5-binding chemokines, such as CCL-3, and migration towards secondary lymphatics in response to CCR7-binding chemokines, such as CCL-19 (Caux et al., 2002;Sallusto et al., 1998;Sozzani et al., 1998); alterations in chemokine release also occur (Piqueras et al., 2006). DC chemotaxis is targeted during immune evasion by vaccinia virus, human cytomegalovirus (HCMV), herpes simplex virus (HSV) and influenza A virus (Humrich et al., 2007;Moutaftsi et al., 2004;Prechtel et al., 2005;Salentin e...

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Impaired Lymphoid Chemokine-Mediated Migration due to a Block on the Chemokine Receptor Switch in Human Cytomegalovirus-Infected Dendritic Cells

Cited by 55 publications

References 36 publications

Infection of mature dendritic cells with herpes simplex virus type 1 dramatically reduces lymphoid chemokine-mediated migration

Infection of mature dendritic cells with herpes simplex virus type 1 dramatically reduces lymphoid chemokine-mediated migration

Hepatitis C virus E2 and CD81 interaction may be associated with altered trafficking of dendritic cells in chronic hepatitis C†

Measles virus modulates chemokine release and chemotactic responses of dendritic cells

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