Human cytomegalovirus inhibits the migration of immature dendritic cells by down-regulating cell-surface CCR1 and CCR5

Varani, Stefania; Frascaroli, Giada; Homman-Loudiyi, Mohammed; Feld, Sari; Landini, Maria Paola; Söderberg‐Nauclér, Cecilia

doi:10.1189/jlb.0504301

Cited by 74 publications

(70 citation statements)

References 47 publications

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“…In contrast, MVA was not capable of inducing such an inflammatory response in immature DC. Interestingly, such a moderate secretion of inflammatory chemokines was also observed by other groups after infection of DC with cytomegalovirus [55], suggesting that this might reflect a general pattern of an anti-viral immune response.…”

Section: Discussionsupporting

confidence: 62%

Vaccinia virus impairs directional migration and chemokine receptor switch of human dendritic cells

Humrich¹,

Thumann²,

Greiner³

et al. 2007

Eur J Immunol

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A crucial event for the induction of an anti-viral immune response is the coordinated, phenotype-dependent migration of dendritic cells (DC) to sites of infection and secondary lymphoid organs. Here we show that the vaccinia virus (VV) strains Western Reserve (WR) and modified virus Ankara (MVA) inhibit directional migration of mature DC toward the lymphoid chemokines CCL19 and CXCL12 without affecting surface expression of the respective chemokine receptors or impairing undirected cellular locomotion. Instead, infection with VV results in a deficiency of extracellular signalregulated kinase-1 and a disturbance of intracellular calcium mobilization, indicating a viral interference with signaling events downstream of the surface chemokine receptors. In immature DC, apart from inhibiting chemokine-induced migration of infected DC, infection with both VV strains increases expression of the inflammatory chemokine receptors CCR1 and CXCR1 on non-infected bystander DC, which depends on the activity of IFN-a. Although functional, these chemokine receptors are resistant to lipopolysaccharide-induced down-regulation. In addition, VV-infected and noninfected bystander DC fail to up-regulate the lymphoid chemokine receptor CCR7 upon activation, together pointing to a disability to undergo the chemokine receptor switch. This study shows that VV targets directional migration of professional antigenpresenting cells at multiple functional levels, revealing a potent viral strategy of immune escape.See accompanying commentary: http://dx

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Section: Discussionsupporting

confidence: 62%

Vaccinia virus impairs directional migration and chemokine receptor switch of human dendritic cells

Humrich¹,

Thumann²,

Greiner³

et al. 2007

Eur J Immunol

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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%

“…Importantly, inhibition of DC migration by human cytomegalovirus (HCMV) has been proposed as a potential viral strategy to paralyze the host's immune response. 11 Dendritic cells display specific trafficking properties. Recruitment of immature DC (imDC) to sites of inflammation is regulated by chemotactic agonists such as the chemokines RANTES, MIP-1␣, and MIP-1␤, which are produced early in inflammatory tissues.…”

mentioning

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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“…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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Human cytomegalovirus inhibits the migration of immature dendritic cells by down-regulating cell-surface CCR1 and CCR5

Cited by 74 publications

References 47 publications

Vaccinia virus impairs directional migration and chemokine receptor switch of human dendritic cells

Vaccinia virus impairs directional migration and chemokine receptor switch of human dendritic cells

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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