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

作者：Baldez Vasconcelos Barbara Cristina; Vieira Juliana Almeida; Silva Geane Oliveira; Fernandes Taiany Nogueira; Rocha Luciano Chaves; Viana Andre Pereira; Sa Serique Cassio Diego; Santos Filho Carlos; Ribeiro Bringel Raissa Aires; Dacier Lobato Teixeira Francisco Fernando; Ferreira Milene Silveira; Moraes Casseb Samir Mansour; Carvalho Valeria Lima; Lopes de Melo Karla Fabiane; Gomes de Castro Paulo Henrique; Araujo Sanderson Correa; Picanco Diniz Jose Antonio; Demachki Samia

来源：Neuropathology, 2016, 36(1): 3-16.

DOI：10.1111/neup.12229

• dengue virus infection
• exacerbated inflammatory response
• microglial morphology
• non-human primate and host inflammatory response

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, TNF. 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 TNF-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.

• 出版日期2016-2