Use este identificador para citar ou linkar para este item:
https://www.arca.fiocruz.br/handle/icict/10550
Tipo de documento
ArtigoDireito Autoral
Acesso restrito
Coleções
- BA - IGM - Artigos de Periódicos [3674]
- INI - Artigos de Periódicos [3460]
- IOC - Artigos de Periódicos [12642]
Metadata
Mostrar registro completo
EMERGING CONCEPTS IN DENGUE PATHOGENESIS: INTERPLAY BETWEEN PLASMABLASTS, PLATELETS, AND COMPLEMENT IN TRIGGERING VASCULOPATHY
Autor(es)
Afiliação
University of Pittsburgh. Center for Vaccine Research. Departments of Infectious Diseases and Microbiology. Pittsburgh, PA, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Instituto de Pesquisa Clinica Evandro Chagas. Rio de Janeiro, RJ, Brasil.
University of Pittsburgh.Department of Otolaringology. Pittsburgh, PA, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.
University of Pittsburgh. Center for Vaccine Research. Departments of Infectious Diseases and Microbiology. Pittsburgh, PA, USA / Fundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Departamento de Virologia e Terapia Experimental. Recife, PE, Brasil.
University of Pittsburgh. Center for Vaccine Research. Departments of Infectious Diseases and Microbiology. Pittsburgh, PA, USA /
University of Pittsburgh. Department pf Immunology. Pittsburgh, PA, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Instituto de Pesquisa Clinica Evandro Chagas. Rio de Janeiro, RJ, Brasil.
University of Pittsburgh.Department of Otolaringology. Pittsburgh, PA, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.
University of Pittsburgh. Center for Vaccine Research. Departments of Infectious Diseases and Microbiology. Pittsburgh, PA, USA / Fundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Departamento de Virologia e Terapia Experimental. Recife, PE, Brasil.
University of Pittsburgh. Center for Vaccine Research. Departments of Infectious Diseases and Microbiology. Pittsburgh, PA, USA /
University of Pittsburgh. Department pf Immunology. Pittsburgh, PA, USA.
Resumo em Inglês
Dengue is a mosquito-borne disease caused by infection with dengue virus (DENV) that represents a
serious and expanding global health threat. Most DENV infections are inapparent or produce mild and self-limiting
illness; however a significant proportion results in severe disease characterized by vasculopathy and plasma leakage
that may culminate in shock and death. The cause of dengue-associated vasculopathy is likely to be multifactorial
but remains essentially unknown. Severe disease is manifest during a critical phase from 4 to 7 days after onset of
symptoms, once the virus has disappeared from the circulation but before the peak of T-cell activation, suggesting
that other factors mediate vasculopathy. Here, we present evidence for a combined role of plasmablasts, complement,
and platelets in driving severe disease in DENV infection. Massive expansion of virus-specific plasmablasts
peaks during the critical phase of infection, coincident with activation of complement and activation and depletion of
platelets. We propose a step-wise model in which virus-specific antibodies produced by plasmablasts form immune
complexes, leading to activation of complement and release of vasoactive anaphylatoxins. Platelets become activated
through binding of complement- and antibody-coated virus, as well as direct binding of virus to DC-SIGN, leading
to the release of inflammatory microparticles and cytokines and sequestration of platelets in the microvasculature.
We suggest that the combined effects of anaphylatoxins, inflammatory microparticles, and platelet sequestration
serve as triggers of vasculopathy in severe dengue.
Compartilhar