RESUMO
Twenty-one pigs inoculated with a highly virulent isolate (E70) of African swine fever (ASF) virus were killed 1-7 days later; a further three animals served as uninfected controls. An early increase in TNF-alpha, IL-1alpha, IL-1beta and IL-6 expression was detected in lymphoid organs from infected animals, together with an increase in the serum concentrations of TNF-alpha and IL-1beta. These changes were accompanied by increased apoptosis of lymphocytes, and the presence of infected and uninfected macrophages showing changes indicative of secretory and phagocytic activation. The present study demonstrated an increase in the number of macrophages expressing TNF-alpha, IL-1 and IL-6 in proximity to lymphocytes undergoing apoptosis, supporting previous suggestions that in acute ASF proinflammatory cytokines induce lymphocyte apoptosis.
Assuntos
Febre Suína Africana/imunologia , Apoptose/imunologia , Asfarviridae/patogenicidade , Citocinas/biossíntese , Linfócitos/imunologia , Tecido Linfoide/imunologia , Febre Suína Africana/patologia , Animais , Asfarviridae/fisiologia , Contagem de Células , Feminino , Marcação In Situ das Extremidades Cortadas , Linfonodos/imunologia , Linfonodos/virologia , Linfócitos/ultraestrutura , Tecido Linfoide/virologia , Ativação de Macrófagos/fisiologia , Macrófagos/imunologia , Macrófagos/ultraestrutura , Macrófagos/virologia , Masculino , Baço/imunologia , Baço/virologia , Suínos , Timo/imunologia , Timo/virologiaRESUMO
Monocytes-macrophages, the target cells of African swine fever virus (ASFV) are highly heterogeneous in phenotype and function. In this study, we have investigated the correlation between the phenotype of specific populations of porcine macrophages and their permissiveness to ASFV infection. Bone marrow cells and fresh blood monocytes were less susceptible to in vitro infection by ASFV than more mature cells, such as alveolar macrophages. FACS analyses of monocytes using a panel of mAbs specific for porcine monocyte/macrophages showed that infected cells had a more mature phenotype, expressing higher levels of several macrophage specific markers and SLA II antigens. Maturation of monocytes led to an increase in the percentage of infected cells, which correlated with an enhanced expression of CD163. Separation of CD163+ and CD163- monocytes demonstrated the specific sensitivity of the CD163+ subset to ASFV infection. In vivo experiments also showed a close correlation between CD163 expression and virus infection. Finally, mAb 2A10 and, in a lower extent, mAb 4E9 were able to inhibit, in a dose-dependent manner, both ASFV infection and viral particle binding to alveolar macrophages. Altogether, these results strongly suggest a role of CD163 in the process of infection of porcine monocytes/macrophages by ASFV.