RESUMO
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.
Assuntos
Células Matadoras Naturais/imunologia , Vírus Elevador do Lactato Desidrogenase/imunologia , Vírus Oncolíticos/imunologia , Plasmocitoma/imunologia , Plasmocitoma/prevenção & controle , Animais , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos KnockoutAssuntos
Infecções por Arterivirus/patologia , Interferon gama/fisiologia , Vírus Elevador do Lactato Desidrogenase/patogenicidade , Animais , Infecções por Arterivirus/metabolismo , Viroses do Sistema Nervoso Central/virologia , Citocinas/metabolismo , Epitopos/química , Inflamação , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Replicação ViralRESUMO
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.
Assuntos
Infecções por Arterivirus/imunologia , Células Matadoras Naturais/imunologia , Vírus Elevador do Lactato Desidrogenase/imunologia , Animais , Infecções por Arterivirus/sangue , Infecções por Arterivirus/virologia , Biomarcadores , Citotoxicidade Imunológica , Expressão Gênica , Integrina alfa2 , Interferon gama/biossíntese , Interferon gama/sangue , Interferon gama/genética , Células Matadoras Naturais/citologia , Contagem de Linfócitos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos CBA , Camundongos Endogâmicos DBA , Camundongos Knockout , Camundongos SCID , Peritônio/citologia , Receptores de Interferon/genética , Baço/citologia , Viremia , Receptor de Interferon gamaRESUMO
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.
