Antibody-enhanced dengue disease generates a marked CNS inflammatory response in the black-tufted marmoset Callithrix penicillata

• Autor(a) principal: Vasconcelos, Barbara Cristina Baldez
• Data de Publicação: 2016
• Outros Autores: Vieira, Juliana Almeida, Silva, Geane Oliveira, Fernandes, Taiany Nogueira, Rocha, Luciano Chaves, Viana, André Pereira, Serique, Cássio Diego Sá, Santos Filho, Carlos, Bringel, Raissa Aires Ribeiro, Teixeira, Francisco Fernando Dacier Lobato, Ferreira, Milene Silveira, Casseb, Samir Mansour Moraes, Carvalho, Valeria Lima, Melo, Karla Fabiane Lopes de, Castro, Paulo Henrique Gomes de, Araújo, Sanderson Corrêa, Diniz Junior, José Antônio Picanço, Demachki, Sâmia, Anaissi, Ana Karyssa Mendes, Sosthenes, Marcia Consentino Kronka, Vasconcelos, Pedro Fernando da Costa, Anthony, Daniel Clive, Diniz, Cristovam Wanderley Picanço, Diniz, Daniel Guerreiro
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Digital do Instituto Evandro Chagas (Patuá)
• Texto Completo: http://patua.iec.gov.br/handle/iec/2425
• topic: Vírus da Dengue / imunologia; Dengue / patologia; Microglia / patologia; Hipocampo / patologia; Inflamação / patologia; Sistema Nervoso Central / patologia; Fator de Necrose Tumoral alfa / metabolismo; Antígenos Virais; Imuno-Histoquímica / métodos; Reação em Cadeia da Polimerase Via Transcriptase Reversa / métodos

Severe dengue disease is often associated with long-term neurological impairments, but it is unclear what mechanisms are associated with neurological sequelae. Previously, we demonstrated antibody-enhanced dengue disease (ADE) dengue in an immunocompetent mouse model with a dengue virus 2 (DENV2) antibody injection followed by DENV3 virus infection. Here we migrated this ADE model to Callithrix penicillata. To mimic human multiple infections of endemic zones where abundant vectors and multiple serotypes co-exist, three animals received weekly subcutaneous injections of DENV3 (genotype III)-infected supernatant of C6/36 cell cultures, followed 24h later by anti-DENV2 antibody for 12 weeks. There were six control animals, two of which received weekly anti-DENV2 antibodies, and four further animals received no injections. After multiple infections, brain, liver, and spleen samples were collected and tissue was immunolabeled for DENV3 antigens, ionized calcium binding adapter molecule 1, Ki-67, TNFa. There were marked morphological changes in the microglial population of ADE monkeys characterized by more highly ramified microglial processes, higher numbers of trees and larger surface areas. These changes were associated with intense TNFa-positive immunolabeling. It is unclear why ADE should generate such microglial activation given that IgG does not cross the blood-brain barrier, but this study reveals that in ADE dengue therapy targeting the CNS host response is likely to be important.