The Role of Heterotypic DENV-specific CD8 + T Lymphocytes in an Immunocompetent Mouse Model of Secondary Dengue Virus Infection

BATALLE, JUAN P.; FERRETTI, ADRIÁN; SIMONETTO, CARLA; ACOSTA, PATRICIO L.; IBAÑEZ, LORENA I.; DAMONTE, ELSA B.; TALARICO, LAURA B.; BRAHAMIAN, JORGE M.; MAURI, ALDANA; LAWRENCE, ANDREA; PAREDES ROJAS, YÉSICA; REY, FÉLIX A.; POLACK, FERNANDO P.; TALARICO, LAURA B.; BRAHAMIAN, JORGE M.; MAURI, ALDANA; LAWRENCE, ANDREA; PAREDES ROJAS, YÉSICA; REY, FÉLIX A.; POLACK, FERNANDO P.; BYRNE, ALANA B.; GARCÍA, AYELÉN G.; HIJANO, DIEGO R.; CABALLERO, MAURICIO T.; MELENDI, GUILLERMINA A.; HARRIS, EVA; BYRNE, ALANA B.; GARCÍA, AYELÉN G.; HIJANO, DIEGO R.; CABALLERO, MAURICIO T.; MELENDI, GUILLERMINA A.; HARRIS, EVA; BATALLE, JUAN P.; FERRETTI, ADRIÁN; SIMONETTO, CARLA; ACOSTA, PATRICIO L.; IBAÑEZ, LORENA I.; DAMONTE, ELSA B.

EBioMedicine

ELSEVIER

Año: 2017 vol. 20 p. 202 - 216

2352-3964

Dengue is the most prevalent arthropod-borne viral disease worldwide and is caused by the four dengue virus serotypes (DENV-1-4). Sequential heterologous DENV infections can be associated with severe disease manifestations. Here, we present an immunocompetent mouse model of secondary DENV infection using non mouse-adapted DENV strains to investigate the pathogenesis of severe dengue disease. C57BL/6 mice infected sequentially with DENV-1 (strain Puerto Rico/94) and DENV-2 (strain Tonga/74) developed low platelet counts, internal hemorrhages, and increase of liver enzymes. Cross-reactive CD8+ T lymphocytes were found to be necessary and sufficient for signs of severe disease by adoptively transferring of DENV-1-immune CD8+T lymphocytes before DENV-2 challenge. Disease signs were associated with production of tumor necrosis factor (TNF)-α and elevated cytotoxicity displayed by heterotypic anti-DENV-1 CD8+ T lymphocytes. These findings highlight the critical role of heterotypic anti-DENV CD8+ T lymphocytes in manifestations of severe dengue disease.