FcγRII-dependent sensitisation of natural interferon-producing cells for viral infection and interferon-α responses

Abstract

Natural interferon-producing cells (NIPC), also called plasmacytoid dendritic cells, are the most potent producers of IFN-a in response to viral and bacterial components,s serving an important function in innate immune defences. The present work demonstrates that NIPC responsiveness can be primed by immunisation, increasing their capacity to produce IFN-a after viral infection. NIPC isolated from pigs immunised against classical swine fever virus (CSFV), a member of the Flaviviridae, were more receptive to viral infection and produced higher levels of IFN-a than NIPC from immunologically naive animals. This sensitisation of NIPC was maintained for at least 8 months after immunisation. IFN-a production was dependent on live virus and required replication, and the "immune" NIPC responded to lower infectious doses of virus. Co-localisation of the virus with FccRII (CD32) in polarised structures was observed with "immune" NIPC only. This FccRII-dependent virus capture and sensitisation of NIPC, evidently mediated through cytophilic CSFV-specific antibodies, was inhibited by non-specifically aggregated immunoglobulin as well as by pre-formed virus-antibody complexes. In conclusion, these results demonstrate that NIPC not only represent a major player in innate immunity but are also functionally linked to the immunological memory of the adaptive immune system.

Classical swine fever virus induces activation of plasmacytoid and conventional dendritic cells in tonsil, blood, and spleen of infected pigs

“…These data also showed that cDC, unlike pDC, disappeared permanently from blood after infection, preventing an efficient turn-over of these DC subset in the spleen. This observation was in agreement with in vitro studies showing that mo-DC functionalities were more affected than NIPC by CSFV infection [4,13]. DC maturation after viral stimulation, demonstrated by down-regulation of CD1a expression and up-regulation of CD80/86 expression [12,15,31], was observed in both DC types.…”

“…In blood, jagged variations in frequencies of pDC expressing cytokines illustrated the pDC turnover presented above. These results were in agreement with cytokine production by in vitro CSFV-infected NIPC [4,42]. Moreover, porcine blood-isolated NIPC secreted IFN-α, TNF-α and IL-12, but not IL-10, after CpGoligonucleotide stimulation [20].…”

“…plasmacytoid DC (pDC). It was shown that CSFV replicates in mo-DC without cytopathological effect but prevents their activation and thereby the secretion of IFN-α, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10 and IL-12 [4,13]. CSFV also blocks mo-DC maturation by inhibiting MHC-II up-regulation, although these cells remain able to present E2 viral envelop glycoprotein to cytotoxic T lymphocytes [14].…”

“…CSFV also blocks mo-DC maturation by inhibiting MHC-II up-regulation, although these cells remain able to present E2 viral envelop glycoprotein to cytotoxic T lymphocytes [14]. Similarly, CSFV replicates in NIPC [4]. However, unlike mo-DC, in vitro infected NIPC secrete large amounts of IFN-α.…”

Induction of Type I IFN Is a Physiological Immune Reaction to Apoptotic Cell-Derived Membrane Microparticles

“…Despite this, only a few studies have investigated their actual role in the immune response. These studies defined pDC as vital cellular components in the initiation of NK and T cell responses to viral Ags (11,12), effectors in the memory response to microbial Ags, where Ag-specific IgG is a prerequisite for pDC activation (13,14), important mediators of transplant tolerance (15)(16)(17)(18), and inducers of T regulatory cells (19,20).…”