Functional disruption of dendritic cells (DCs) is an important strategy for viral pathogens to evade host defences. Monocytotropic viruses such as classical swine fever virus (CSFV) could employ such a mechanism, since the virus can suppress immune responses and induce apoptosis without infecting lymphocytes. Here, CSFV was shown to infect and efficiently replicate in monocyte-and in bone marrow-derived DCs. Interestingly, the infected DCs displayed neither modulated MHC nor CD80/86 expression. Stimulation of DCs with IFN-a/TNF-a or polyinosinic-polycytidylic acid (pIC) induced phenotypic maturation with increased MHC and CD80/86 expression, both with mock-treated and infected DCs. In addition, the T cell stimulatory capacity of CSFV-infected DCs was maintained both in a polyclonal T cell stimulation and in specific antigen-presentation assays, requiring antigen uptake and processing. Interestingly, similar to macrophages, CSFV did not induce IFN-a responses in these DCs and even suppressed pIC-induced IFN-a induction. Other cytokines including interleukin (IL)-6, IL-10, IL-12 and TNF-a were not modulated. Taken together, these results demonstrated that CSFV can replicate in DCs and control IFN type I responses, without interfering with the immune reactivity. These results are interesting considering that DC infection with RNA viruses usually results in DC activation.
INTRODUCTIONClassical swine fever (CSF) is a highly contagious disease of pigs caused by CSF virus (CSFV) and leads to important economic losses worldwide. CSFV together with bovine viral diarrhoea virus (BVDV) and border disease virus (BDV) form the genus Pestivirus within the family Flaviviridae.CSFV is a monocytotropic viral pathogen, which can efficiently evade and compromise the host's immune system. The virus has a high affinity for reticulo-endothelial cells (Cheville & Mengeling, 1969;Ressang, 1973;Susa et al., 1992) causing lymphopenia, thrombocytopenia, coagulation disorders and atrophy of the thymus and bone marrow Pauly et al., 1998; Sanchez-Cordon et al., 2002;Summerfield et al., 2000Summerfield et al., , 2001. Lymphopenia is caused, at least in part, by apoptosis detectable in uninfected lymphocytes Summerfield et al., 1998b). In addition, viable lymphocytes isolated from CSFV-infected pigs do not respond to mitogen stimulation (Pauly et al., 1998;Summerfield et al., 1998b;Van Oirschot et al., 1983). These modulated cells are not infected. Instead, it is the myeloid population, particularly monocytes (Mo) and macrophages (Mw), that contains the early target cell for infection and replication, both in vivo (Ressang, 1973;Gomez-Villamandos et al., 2001;Sanchez-Cordon et al., 2003;Summerfield et al., 2000;Trautwein, 1988) and in vitro (Knoetig et al., 1999). Despite this clear targeting and tropism, no direct evidence has been found of a role for infected Mo and Mw in the observed immunosuppression and death of T lymphocytes (Knoetig et al., 1999).Dendritic cells (DCs) are one of the primary immunological sentinels of the immune system ...