RESUMEN
Although many cells undergo transformation, few actually develop into tumours, due to successful mechanisms of immunosurveillance. To investigate whether an infectious agent may play a role in this process, the growth of a plasmacytoma was investigated in mice infected by lactate dehydrogenase-elevating virus. Acutely infected animals were significantly protected against tumour development. The mechanisms responsible for this protection were analysed in mice deficient for relevant immune cells or molecules and after in vivo cell depletion. This protection by viral infection correlated with NK cell activation and with IFN-γ production. It might also be related to activation of NK/T-cells, although this remains to be proven formally. Therefore, our results indicated that infections with benign micro-organisms may protect the host against cancer development, through non-specific stimulation of the host's innate immune system and especially of NK cells.
Asunto(s)
Células Asesinas Naturales/inmunología , Virus Elevador de Lactato Deshidrogenasa/inmunología , Virus Oncolíticos/inmunología , Plasmacitoma/inmunología , Plasmacitoma/prevención & control , Animales , Modelos Animales de Enfermedad , Femenino , Ratones , Ratones Endogámicos BALB C , Ratones NoqueadosAsunto(s)
Infecciones por Arterivirus/patología , Interferón gamma/fisiología , Virus Elevador de Lactato Deshidrogenasa/patogenicidad , Animales , Infecciones por Arterivirus/metabolismo , Enfermedades Virales del Sistema Nervioso Central/virología , Citocinas/metabolismo , Epítopos/química , Inflamación , Macrófagos/metabolismo , Ratones , Ratones Endogámicos BALB C , Replicación ViralRESUMEN
Early after infection, lactate dehydrogenase-elevating virus (LDV) alters the immune system by polyclonally activating B lymphocytes, which leads to IgG2a-restricted hypergammaglobulinaemia, and by suppressing the secretion of Th2 cytokines. Considering that these alterations may involve cells of the innate immune system and cytokines such as interferon-gamma (IFN-gamma), we analysed the effect of LDV on natural killer (NK) cells. Within a few days of infection, a strong and transient NK cell activation, characterized by enhanced IFN-gamma message expression and cytolysis, was observed. LDV triggered a large increase in serum IFN-gamma levels. Because NK cells and IFN-gamma may participate in the defence against virus infection, we analysed their possible role in the control of LDV titres with a new agglutination assay. Our results indicate that neither the activation of NK cells nor the IFN-gamma secretion affect the early and rapid virus replication that follows LDV inoculation.
Asunto(s)
Infecciones por Arterivirus/inmunología , Células Asesinas Naturales/inmunología , Virus Elevador de Lactato Deshidrogenasa/inmunología , Animales , Infecciones por Arterivirus/sangre , Infecciones por Arterivirus/virología , Biomarcadores , Citotoxicidad Inmunológica , Expresión Génica , Integrina alfa2 , Interferón gamma/biosíntesis , Interferón gamma/sangre , Interferón gamma/genética , Células Asesinas Naturales/citología , Recuento de Linfocitos , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos CBA , Ratones Endogámicos DBA , Ratones Noqueados , Ratones SCID , Peritoneo/citología , Receptores de Interferón/genética , Bazo/citología , Viremia , Receptor de Interferón gammaRESUMEN
Immunoglobulin G1 (IgG1), IgG2a, and IgG2b switch variants were derived from an IgG3 monoclonal antibody directed against the VP3 envelope glycoprotein of lactate dehydrogenase-elevating virus (LDV). Among the four antibodies, IgG2a delayed the onset and progression of LDV-induced polioencephalomyelitis more than did the other subclasses. This suggests that the IgG2a predominance observed in many IgG antibody responses elicited by live viruses could, at least under some circumstances, correspond to the selection of the best protection for the infected host.
