Immunopathogenesis of classical swine fever: role of monocytic cells

Abstract

SUMMARYVirulent classical swine fever (CSF ) represents an immunomodulatory viral infection that perturbs immune functions. Circulatory and immunopathological disorders include leukopenia, immunosuppression and haemorrhage. Monocytic cells -targets for CSF virus (CSFV ) infection -could play critical roles in the immunopathology, owing to their production of immunomodulatory and vasoactive factors. Monocytes and macrophages (Mw) are susceptible to virus infection, as a consequence of which prostaglandin E 2 (PGE 2 ) production is enhanced. The presence of PGE 2 in serum from CSFV-infected pigs correlated with elevated PGE 2 productivity by the peripheral blood mononuclear cells from these same animals. It was noted that these PGE 2 -containing preparations did not inhibit, but actually enhanced, lymphocyte proliferation. The proinflammatory cytokines tumour necrosis factor-a (TNF-a) and interleukin (IL)-6 were not involved, although elevated IL-1 production could relate to lymphocyte activation. Nevertheless, IL-1 was not the sole element: infected Mw produced lympho-stimulatory activity but little IL-1. This release of immunomodulatory factors, following CSFV infection of monocytic cells, was compared with other characteristics of the disease. Therein, PGE 2 and IL-1 production was noted to coincide with the onset of fever and the coagulation disorders typical of CSF. Consequently, these factors are of greater relevance to the haemorrhagic disturbances, such as petechia and infarction, rather than the leukopenia found in CSF.

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

“…Indeed, TNF-α and IFN-α can have adverse effects when produced in huge amounts after viral infection [32]. Thus, it was suggested that TNF-α secreted by CD172a + cells, together with IL-1, IL-6 and prostaglandin, were responsible for apoptosis in non-infected immune system cells in lymphoid organs [16,24,38]. These authors implicated macrophages as TNF-α producing cells, but our data showed that DC could also play a role in this phenomenon.…”

Immunological properties of recombinant classical swine fever virus NS3 protein in vitro and in vivo

“…Cell associated virus was released by sonificating the cells and clarification of the cell lysates as described [17]. For mock controls, clarified lysates of uninfected cells were employed.…”

“…For mock controls, clarified lysates of uninfected cells were employed. Virus titres were determined by endpoint dilution titrations on SK-6 cells as described previously [17].…”

“…Virus titres of serum samples were determined by endpoint dilution titrations [17]. The detection limit of the assay was 10 1.5 TCID 50 /mL.…”

Cholera toxin promotes the generation of semi-mature porcine monocyte-derived dendritic cells that are unable to stimulate T cells

“…MoDC cultures were pulsed with the following antigens for 26 h, with Ctx added after 2 h if required: (1) CSFV strain Alfort (0.01 TCID 50 /cell), (2) mock antigen prepared from uninfected SK6 cells used to propagate the virus [27], (3) E2-protein of CSFV, baculovirus-expressed (4 µg/mL) produced as described elsewhere [36], or (4) CSFV-non-structural protein 3 (NS3)-protein of CSFV, E. coli-expressed (2 µg/mL; kindly provided by Dr Hilde Revets, Free University Brussels, Belgium). MoDC were then co-cultured with autologous lymphocytes in the presence of the respective antigens for 3-4 days, and analysis of [ 3 H]methyl-thymidine incorporation was performed as described above.…”