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|Title:||Emerging Concepts in Dengue Pathogenesis: Interplay between Plasmablasts, Platelets, and Complement in Triggering Vasculopathy|
|Authors:||Nascimento, Eduardo J. M|
Hottz, Eugenio D
Bates, Tatiana M. Garcia
Marques, Ernesto T. A
Boyes, Simon M. Barratt
|Affilliation:||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.
|Abstract:||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.|
|Keywords in spanish:||Dengue|
|Publisher:||Begell House, Inc|
|Citation:||NASCIMENTO, Eduardo J. M. et al. Emerging Concepts in Dengue Pathogenesis: Interplay between Plasmablasts, Platelets, and Complement in Triggering Vasculopathy. Critical Reviews™ in Immunology, v.34, n.3, p.227–240, 2014.|
|Appears in Collections:||INI - Artigos de Periódicos|
BA - IGM - Artigos de Periódicos
IOC - Artigos de Periódicos
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