Human herpesvirus 6 (HHV-6) is a potentially immunosuppressive CD4 +-T-lymphotropic betaherpesvirus that causes severe human thymocyte depletion in heterochimeric SCID-hu thy/liv mice and has been implicated as a potential cofactor in the progression of AIDS. However, the mechanisms of HHV-6-mediated immunosuppression have not yet been fully elucidated. We investigated the phenotypic and functional alterations induced by HHV-6 on peripheral blood-derived human dendritic cells (DC). The infection of DC with HHV-6 A or B was nonproductive, as revealed by calibrated real-time PCR measuring the accumulation of viral genome equivalents over time. Nevertheless, preexposure to HHV-6 markedly impaired the maturation of DC driven by gamma interferon and lipopolysaccharide, as shown by the reduced surface expression of major histocompatibility complex class 1 molecules, HLA-DR, CD40, and CD80. Moreover, HHV-6, but not the closely related betaherpesvirus HHV-7, dramatically suppressed the secretion of interleukin-12 (IL-12) p70 by DC, while the production of other cytokines that influence DC maturation, i.e., IL-10 and tumor necrosis factor alpha, was not significantly modified. Likewise, the secretion of the CC chemokines macrophage inflammatory protein 1(beta) and RANTES was unaltered. Functionally, a pretreatment with HHV-6 impaired the ability of DC to stimulate allogeneic T-cell proliferation. Altogether, these data identify interference with the functional maturation of DC as a potential mechanism of HHV-6-mediated immunosuppression.
|Titolo:||Viral replication-independent blockade of dendritic cell maturation and interleukin-12 production by human herpesvirus 6|
|Autori interni:||SANTORO, FRANCO|
|Parole Chiave:||human herpesvirus 6; SCID mouse; T lymphocyte; acquired immune deficiency syndrome; animal experiment; animal model; animal tissue; antigen expression; article; cell differentiation; cell maturation; controlled study; cytokine production; dendritic cell; flow cytometry; human cell; human; lymphocyte proliferation; mouse; nonhuman; priority journal; real time polymerase chain reaction; virus replication; B7 antigen; CD40 antigen; HLA DR antigen; RANTES; beta chemokine; gamma interferon; interleukin 10; interleukin 12; interleukin 12p70; lipopolysaccharide; macrophage inflammatory protein 1beta; major histocompatibility antigen class 1; tumor necrosis factor alpha; unclassified drug|
|Settore Scientifico Disciplinare:||Settore MED/28 - Malattie Odontostomatologiche|
|Data di pubblicazione:||mar-2005|
|Digital Object Identifier (DOI):||10.1128/JVI.79.5.2807-2813.2005|
|Appare nelle tipologie:||01 - Articolo su periodico|