title: Classical swine fever virus suppresses maturation and modulates functions of monocyte-derived dendritic cells without activating nuclear factor kappa B.
abstract: Classical swine fever virus (CSFV) compromises the host immune system, causing the severe disease of pigs. Dendritic cells (DCs) are the most potent inducers of immune responses. In the present study, we investigated the functional properties of porcine monocyte-derived DCs (Mo-DCs) affected by CSFV. Results showed that the expression of surface markers of DCs such as major histocompatibility complex class II (MHC-II), CD80, CD83 and CD86 were unimpaired, but an obviously increased expression of CD172a in DCs was noticed 48 h after CSFV infection. The expression profiles of cytokines were detected in cultured Mo-DCs after various treatments for 48 h by Q-RT-PCR. The findings suggested that CSFV infection significantly increased the mRNA expression of IL-10 and TNF-α, and inhibited IL-12 expression, with little effect on IFN-α and IFN-γ expression. We further demonstrated that CSFV was incapable of activating the nuclear factor kappa B (NF-κB) in infected DCs, which was characterized by an unvaried DNA binding activity of NF-κB, the lack of translocation of p65/RelA from the cytoplasm to the nucleus and the stabilization of p65/RelA expression. Furthermore, Western blot analysis indicated that the inactivation of NF-κB was due to the failure of IκBα degradation. The data demonstrated that CSFV could be replicated in DCs and CSFV infection could modulate the secretion of crucial co-stimulatory molecules and cytokines which down-regulated maturation of DCs, without activating NF-κB in DCs. Thus, the results suggested a possible mechanism for CSFV evasion of innate host defenses, providing the basis for understanding molecular pathways in CSFV pathogenesis.
authors.affiliation: College of Veterinary Medicine, South China Agricultural University, 483 Wu Shan Road, Tian He District, Guangzhou 510642, China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Chen
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Dong
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Shen
authors.forename: Ming-Qiu
authors.initials: MQ
authors.lastname: Zhao
authors.forename: Chun-Mei
authors.initials: CM
authors.lastname: Ju
authors.forename: Lin
authors.initials: L
authors.lastname: Yi
authors.forename: Xue-Tao
authors.initials: XT
authors.lastname: Zhang
authors.forename: Yan-Mei
authors.initials: YM
authors.lastname: Kang
authors.forename: Jin-Ding
authors.initials: JD
authors.lastname: Chen
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000662:veterinary; D006691:Classical Swine Fever / Q000276:immunology / Q000503:physiopathology / Q000821:virology*; D006692:Classical Swine Fever Virus / Q000502:physiology*; D003713:Dendritic Cells / Q000502:physiology / Q000821:virology*; D024202:Electrophoretic Mobility Shift Assay / Q000662:veterinary; D005434:Flow Cytometry / Q000662:veterinary; D005455:Fluorescent Antibody Technique / Q000662:veterinary; D016898:Interferon-alpha / Q000502:physiology; D007371:Interferon-gamma / Q000502:physiology; D016753:Interleukin-10 / Q000502:physiology; D018664:Interleukin-12 / Q000502:physiology; D016328:NF-kappa B / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction / Q000662:veterinary; D013552:Swine / Q000276:immunology / Q000821:virology
chemical_list: D016898:Interferon-alpha; D016328:NF-kappa B; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma