Immunopathological mechanisms in dengue and dengue... : Current Opinion in Infectious Diseases (original) (raw)

Tropical and travel-associated diseases

Immunopathological mechanisms in dengue and dengue hemorrhagic fever

University of Massachusetts Medical School, Center for Infectious Disease and Vaccine Research, Worcester, Massachusetts, USA

Correspondence to Alan Rothman, MD, University of Massachusetts Medical School, Center for Infectious Disease and Vaccine Research, 55 Lake Avenue, North Room S5-326, Worcester, MA 01655, USA Tel: +1 508 856 4182; fax: +1 508 856 4890; e-mail: [email protected]

Sponsorship: This work was financially supported by National Institutes of Health grant no. P01 AI1034533.

Abstract

Purpose of review

The continued emergence of dengue virus infection and its severe disease manifestation, dengue hemorrhagic fever, is a growing public health problem. The majority of severe infections occur upon secondary encounters with heterologous dengue virus serotypes, suggesting an immune-mediated process.

Recent findings

Significant findings in the past year include a greater understanding of dengue virus interactions with target cells such as dendritic cells, hepatocytes and endothelial cells. Infection of these cells results in the production of immune mediators that then shape the adaptive humoral and cellular immune response. The circulation of high levels of secreted NS1 in the presence of pre-existing heterologous non-neutralizing antibody may mediate complement activation and trigger plasma leakage. The role of enhancing antibodies in disease pathogenesis remains unclear. Recent studies demonstrate low avidity crossreactive T cells, which may produce an altered profile of cytokines leading to plasma leakage. Ongoing prospective studies that include epidemiological, virological and immunological risk factors are crucial to our understanding of the mechanisms of immunopathogenesis of dengue hemorrhagic fever.

Summary

The immune mechanisms that lead to dengue hemorrhagic fever are complex and need to be elucidated further for the development of therapeutics as well as safe and efficacious dengue vaccines.