Peripheral blood contains two major particular infrequent dendritic cells (DC) subsets linking the innate and specific immune system, the myeloid DC and plasmacytoid DC equivalent to the natural interferon-producing cells (NIPC). The functional characterization of these cells demands large volumes of blood, making a large animal model more appropriate and beneficial for certain studies. Here, two subsets of porcine blood mononuclear cells expressing swine workshop cluster 3 (SWC3, a SIRP family member), are described and compared to monocytes. The blood DC specialized in T-cell stimulation were major histocompatibility complex (MHC) class II+, CD80/86+, CD1+/-, CD4-, and in contrast to monocytes CD14-. A CD16- and a CD16+ subset could be discriminated. Granulocyte-macrophage colony-stimulating factor and interleukin-3 were survival factors for this DC subset, and culture induced an up-regulation of MHC class II and CD80/86. The second subset described, are porcine NIPC, typically CD4++, MHC class IIlow, CD80/86low, CD1-, CD8-/low, CD16-/low and CD45RA-/low. Porcine NIPC had high interleukin-3 binding capacity, and survived in response to this cytokine. Their unique function was strong interferon type I secretion after virus stimulation. Both subsets were endocytically active when freshly isolated, and down-regulated this activity after in vitro maturation. Taken together, the present report has delineated porcine blood DC and NIPC, permitting a more detailed understanding of innate immune defences, particularly in response to infections.
The voltage-gated potassium (Kv) channels, encoded by 40 genes, repolarize all electrically excitable cells, including plant, cardiac, and neuronal cells. Although these genes were fully sequenced decades ago, a comprehensive kinetic characterization of all Kv channels is still missing, especially near physiological temperature. Here, we present a standardized kinetic map of the 40 homomeric Kv channels systematically characterized at 15, 25, and 35°C. Importantly, the Kv kinetics at 35°C differ significantly from commonly reported kinetics, usually performed at room temperature. We observed voltage-dependent Q 10 for all active Kv channels and inherent heterogeneity in kinetics for some of them. Kinetic properties are consistent across different host cell lines and conserved across mouse, rat, and human. All electrophysiology data from all Kv channels are made available through a public website (Channelpedia). This dataset provides a solid foundation for exploring kinetics of heteromeric channels, roles of auxiliary subunits, kinetic modulation, and for building accurate Kv models.
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 ...
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