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Antibody‐enhanced dengue disease generates a marked CNS inflammatory response in the black‐tufted marmoset Callithrix penicillata
Author(s) -
Vasconcelos Barbara Cristina Baldez,
Vieira Juliana Almeida,
Silva Geane Oliveira,
Fernandes Taiany Nogueira,
Rocha Luciano Chaves,
Viana André Pereira,
Serique Cássio Diego Sá,
Filho Carlos Santos,
Bringel Raissa Aires Ribeiro,
Teixeira Francisco Fernando Dacier Lobato,
Ferreira Milene Silveira,
Casseb Samir Mansour Moraes,
Carvalho Valéria Lima,
Melo Karla Fabiane Lopes,
Castro Paulo Henrique Gomes,
Araújo Sanderson Corrêa,
Diniz José Antonio Picanço,
Demachki Samia,
Anaissi Ana Karyssa Mendes,
Sosthenes Marcia Consentino Kronka,
Vasconcelos Pedro Fernando da Costa,
Anthony Daniel Clive,
Diniz Cristovam Wanderley Picanço,
Diniz Daniel Guerreiro
Publication year - 2016
Publication title -
neuropathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.701
H-Index - 61
eISSN - 1440-1789
pISSN - 0919-6544
DOI - 10.1111/neup.12229
Subject(s) - dengue fever , immunolabeling , dengue virus , antibody , biology , immunology , callithrix , flavivirus , virology , population , marmoset , antigen , medicine , virus , immunohistochemistry , environmental health , paleontology
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.