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BIBTEX RIS

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

2015; Wiley; Volume: 36; Issue: 1 Linguagem: Inglês

10.1111/neup.12229

1440-1789

Barbara Cristina Baldez Vasconcelos, Juliana Almeida Vieira, Geane Oliveira Silva, Taiany Nogueira Fernandes, Luciano Chaves Rocha, André Pereira Viana, Cássio Diego Sá Serique, Carlos Santos Filho, Raissa Aires Ribeiro Bringel, Francisco Fernando Dacier Lobato Teixeira, Milene Silveira Ferreira, Samir Mansour Moraes Casseb, Valéria Lima Carvalho, Karla Fabiane Lopes de Melo, Paulo Henrique Gomes de Castro, Sanderson Corrêa Araújo, José Antônio Picanço Diniz, Sâmia Demachki, Ana Karyssa Mendes Anaissi, Márcia Consentino Kronka Sosthenes, Pedro Fernando da Costa Vasconcelos, Daniel C. Anthony, Cristovam Wanderley Picanço Diniz, Daniel Guerreiro Diniz,

Infectious Encephalopathies and Encephalitis

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 24 h 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, TNFα. 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 TNFα‐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.