Antibody-Dependent Enhancement of Dengue Virus Infection in Primary Human Macrophages; Balancing Higher Fusion against Antiviral Responses.

The dogma is that the human immune system protects us against pathogens. Yet, several viruses, like dengue virus, antagonize the hosts' antibodies to enhance their viral load and disease severity; a phenomenon called antibody-dependent enhancement of infection. This study offers novel insights in the molecular mechanism of antibody-mediated enhancement (ADE) of dengue virus infection in primary human macrophages. No differences were observed in the number of bound and internalized DENV particles following infection in the absence and presence of enhancing concentrations of antibodies. Yet, we did find an increase in membrane fusion activity during ADE of DENV infection. The higher fusion activity is coupled to a low antiviral response early in infection and subsequently a higher infection efficiency. Apparently, subtle enhancements early in the viral life cycle cascades into strong effects on infection, virus production and immune response. Importantly, and in contrast to other studies, the antibody-opsonized virus particles do not trigger immune suppression and remain sensitive to interferon. Additionally, this study gives insight in how human macrophages interact and respond to viral infections and the tight regulation thereof under various conditions of infection.

Células con propiedades inmunoreguladoras y su impacto en la patogénesis de la sepsis / Cells with immunoregulatory properties and their impact in the pathogenesis of sepsis

Sepsis, defined as a systemic inflammatory response syndrome caused by an infection, is a significant cause of mortality worldwide. It is currently accepted that death associated to sepsis is due to an immune hyperactivation state involving the development of a broad proinflammatory response along with alterations in the coagulation system. It is now clear that besides the inflammatory events, the clinical course of sepsis is characterized by the development of an anti-inflammatory response that could lead to death in its attempt to balance the initial response. The purpose of this review is to summarize current mechanisms that explain the pathogenesis of sepsis, underlying the role that cells with immunoregulatory properties play during the course of this complex syndrome. A better understanding of these processes will contribute in the search of more successful therapeutic strategies.

El síndrome de respuesta sistémica consecuencia de una infección, denominado sepsis, constituye una causa significativa de muerte en el mundo. Históricamente se ha aceptado que la muerte por sepsis se debe a un estado de hiperactivación inmunológica, que implica el desarrollo de una vasta respuesta pro-inflamatoria acompañada de alteraciones en el sistema de coagulación. Ahora es claro que además de los sucesos inflamatorios, el curso clínico de la sepsis se caracteriza por el desarrollo de una respuesta anti-inflamatoria que busca contrarrestar la respuesta inicial, y es ésta finalmente en gran parte responsable de la muerte de los pacientes. El propósito de esta revisión es resumir los mecanismos actuales que explican la patogénesis de la sepsis, y específicamente el papel que desempeñan las subpoblaciones celulares con propiedades inmuno-reguladoras durante el curso de la enfermedad. El mejor entendimiento de estos procesos contribuirá a la búsqueda de estrategias terapéuticas más exitosas.

[Cells with immunoregulatory properties and their impact in the pathogenesis of sepsis]. / Células con propiedades inmunoreguladoras y su impacto en la patogénesis de la sepsis.

Sepsis, defined as a systemic inflammatory response syndrome caused by an infection, is a significant cause of mortality worldwide. It is currently accepted that death associated to sepsis is due to an immune hyperactivation state involving the development of a broad proinflammatory response along with alterations in the coagulation system. It is now clear that besides the inflammatory events, the clinical course of sepsis is characterized by the development of an anti-inflammatory response that could lead to death in its attempt to balance the initial response. The purpose of this review is to summarize current mechanisms that explain the pathogenesis of sepsis, underlying the role that cells with immunoregulatory properties play during the course of this complex syndrome. A better understanding of these processes will contribute in the search of more successful therapeutic strategies.