HHV-8 reduces dendritic cell migration through down-regulation of cell-surface CCR6 and CCR7 and cytoskeleton reorganization
© Cirone et al.; licensee BioMed Central Ltd. 2012
Received: 10 January 2012
Accepted: 14 May 2012
Published: 14 May 2012
For an efficient immune response against viral infection, dendritic cells (DCs) must express a coordinate repertoire of receptors that allow their recruitment to the sites of inflammation and subsequently to the secondary lymphoid organs in response to chemokine gradients.
Several pathogens are able to subvert the chemokine receptor expression and alter the migration properties of DCs as strategy to escape from the immune control.
Here we report the inhibitory effect of Human Herpesvirus 8 (HHV-8) on the migratory behavior of immature and mature DCs. We found that the virus altered the DC chemokine receptor expression and chemokine induced migration. Moreover HHV-8 was also able to interfere with basal motility of DCs by inducing cytoskeleton modifications.
Based on our findings, we suggest that HHV-8 is able to subvert the DC migration capacity and this represents an additional mechanism which interferes with their immune-functions.
Dendritic cells (DCs) are critical for initiating an adaptive immune response against microbial and tumor antigens . Their function is strictly linked to their migration properties along chemokine gradients and other chemotactic factors . Immature DCs (iDCs) and their precursors are recruited to the infection and inflammatory sites in response to inflammatory chemokines such as MIP1 alfa and beta, CCL5/Rantes and CCL20 which bind to the chemokine receptors CCR1, CCR5, CCR2 and CCR6 respectively [3–5].In the peripheral tissues, DCs can initiate the antigen uptake and processing which, together with the exposure to inflammatory signals, results in DC maturation. This process is followed by switch of the chemokines receptor repertoire, e.g. downregulation of CCR5 and upregulation of CCR7, which drives their migration to secondary lymphoid organs mainly in response to the CCL19 chemokine . To evade immune control, several viruses have been shown to interfere with the migratory capacity of DCs, as well as with their differentiation and maturation process. Vaccinia virus impairs migration and receptor switch of infected and bystander DCs , Human Respiratory Syncitial virus , Herpes Simplex virus  and Cytomegalovirus alter the chemokine-mediated migration by downregulating CCR1, CCR5  and CCR7  chemokine receptors on immature and mature DCs. Human Herpesvirus 8 (HHV-8), an oncogenic virus associated to Kaposi’s Sarcoma and Primary Effusion Lymphoma  has been previously shown to interfere with DC function  and impair the in vitro monocyte differentiation into DCs . Here we asked if HHV-8 is also able to alter the pattern of chemokine receptor expression of monocyte-derived DCs and interfere with their migratory capacity.
This work was partially supported by grants from MIUR, Associazione Italiana per la ricerca sul Cancro (AIRC), progetto strategico ISS 9ACF/1 of Ministero della salute and Pasteur Cenci-Bolognetti foundation.
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