Dengue haemorrhagic fever and dengue shock syndrome: are they tumour necrosis factor-mediated disorders?

Yadav, Manish; Kamath, K. R.; Iyngkaran, N.; Sinniah, M

doi:10.1111/j.1574-6968.1991.tb04969.x

Cited by 45 publications

(33 citation statements)

References 23 publications

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“…5C), suggesting that Fc␥RIIa mediated entry of DV-immune complexes leads to signaling for cytokine production. Cytokine storms are linked to disease severity in severe DV infections, e.g., high serum levels of TNF-␣ in patients suffering from DHF/DSS (52). Identifying a new cellular compartment susceptible to ADE with a capacity for increased viral replication and proinflammatory cytokine release at PENT links key pathogenesis concepts.…”

Section: Discussionmentioning

confidence: 99%

Role of Dendritic Cells in Antibody-Dependent Enhancement of Dengue Virus Infection

Boonnak

Slike

Burgess

et al. 2008

J Virol

175

172

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Dengue viruses (DV), composed of four distinct serotypes (DV1 to DV4), cause 50 to 100 million infections annually. Durable homotypic immunity follows infection but may predispose to severe subsequent heterotypic infections, a risk conferred in part by the immune response itself. Antibody-dependent enhancement (ADE), a process best described in vitro, is epidemiologically linked to complicated DV infections, especially in Southeast Asia. Here we report for the first time the ADE phenomenon in primary human dendritic cells (DC), early targets of DV infection, and human cell lines bearing Fc receptors. We show that ADE is inversely correlated with surface expression of DC-SIGN (DC-specific intercellular adhesion molecule-3-grabbing nonintegrin) and requires Fc gamma receptor IIa (Fc␥RIIa). Mature DC exhibited ADE, whereas immature DC, expressing higher levels of DC-SIGN and similar Fc␥RIIa levels, did not undergo ADE. ADE results in increased intracellular de novo DV protein synthesis, increased viral RNA production and release, and increased infectivity of the supernatants in mature DC. Interestingly, tumor necrosis factor alpha and interleukin-6 (IL-6), but not IL-10 and gamma interferon, were released in the presence of dengue patient sera but generally only at enhancement titers, suggesting a signaling component of ADE. Fc␥RIIa inhibition with monoclonal antibodies abrogated ADE and associated downstream consequences. DV versatility in entry routes (Fc␥RIIa or DC-SIGN) in mature DC broadens target options and suggests additional ways for DC to contribute to the pathogenesis of severe DV infection. Studying the cellular targets of DV infection and their susceptibility to ADE will aid our understanding of complex disease and contribute to the field of vaccine development.

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Section: Discussionmentioning

confidence: 99%

Role of Dendritic Cells in Antibody-Dependent Enhancement of Dengue Virus Infection

Boonnak

Slike

Burgess

et al. 2008

J Virol

175

172

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“…It should also be considered that a report has shown augmented serum TNF-␣ levels in patients suffering dengue hemorrhagic fever͞dengue shock syndrome (DHF͞DSS), compared with patients with primary dengue fever (23). While the serum TNF-␣ levels reported for DHF͞DSS patients were a convincing correlate to the severity of these diseases, ex vivo monocyte͞ macrophage cultures from these patients were not examined directly for spontaneous or in vitro stimulated TNF-␣ production, leaving the question open as to the nature of the cells producing the excessive TNF-␣ concentrations in these patients.…”

Section: Discussionmentioning

confidence: 99%

Suppression of lipopolysaccharide-induced antiviral transcription factor (STAT-1 and NF-κB) complexes by antibody-dependent enhancement of macrophage infection by Ross River virus

Mahalingam

Lidbury²

2002

Proc. Natl. Acad. Sci. U.S.A.

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“…TNF is a potent endothelial cell-activating factor with recognized importance in the pathogenesis of severe dengue disease (1, 10). High levels of TNF in DHF patients are suspected of causing activation or injury of endothelial cells (20,38,39,49). Clinical studies of dengue virus-infected patients have repeatedly found high levels of TNF in serum, with increased levels strongly correlated with the severity of disease (16,20,27).…”

mentioning

confidence: 99%

Dengue Virus Infection of Mast Cells Triggers Endothelial Cell Activation

Brown

Hermann

Issekutz

et al. 2011

J Virol

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Vascular perturbation is a hallmark of severe forms of dengue disease. We show here that antibodyenhanced dengue virus infection of primary human cord blood-derived mast cells (CBMCs) and the human mast cell-like line HMC-1 results in the release of factor(s) which activate human endothelial cells, as evidenced by increased expression of the adhesion molecules ICAM-1 and VCAM-1. Endothelial cell activation was prevented by pretreatment of mast cell-derived supernatants with a tumor necrosis factor (TNF)-specific blocking antibody, thus identifying TNF as the endothelial cell-activating factor. Our findings suggest that mast cells may represent an important source of TNF, promoting vascular endothelial perturbation following antibody-enhanced dengue virus infection.Dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) represent the most life-threatening clinical outcomes of dengue virus infections. The immunopathological mechanisms are significant and include antibody-dependent enhancement of dengue virus infection, a known risk factor in the development of DHF/DSS (18). A major distinguishing feature of DHF/DSS is plasma leakage; therefore, much attention has been directed to mechanisms of vascular endothelial dysfunction. Histological damage to the vascular endothelium in DHF cases is usually limited to swelling and occasional intercellular gaps (41), suggesting that endothelial perturbation is mediated by subtle immunopathological effects rather than by cytopathological virus infection. Dengue virus infection promotes upregulation of membrane-associated and soluble adhesion molecules which are indicative of endothelial cell activation (1, 36). These parameters correlate with disease severity (9,21,25,34,43).Mast cells are connective tissue-associated leukocytes located at areas of external interface, such as the skin and mucous membranes. They are in close proximity to blood vessels, with functional roles in a variety of inflammatory conditions (i.e., asthma and allergy) and innate protection against pathogens. The evidence for mast cell involvement in dengue disease includes observations that dengue patients exhibit increased levels of blood and urinary histamine (a product of mast cells and basophils), which correlates with disease severity (37,47). A large histological study of DHF patients noted that mast cells in the connective tissue around the thymus showed swelling, vacuolation of the cytoplasm, and loss of granule integrity, suggestive of mast cell activation (5). Mast cells are also involved in skin eruptions (rash), a common feature of dengue virus infection (19,35,42,48).We have previously reported that human mast cells are permissive to antibody-enhanced dengue virus infection, occurring in an Fc␥RII-dependent manner (6, 23). Infection of mast cell lines KU812 and HMC-1 results in infectious virus production and the induction of significant levels of cytokines, such as interleukin-1␤ (IL-1␤) and IL-6, as well as chemokines CCL3, CCL4, and CCL5, which can recruit additional immune effector...

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Dengue haemorrhagic fever and dengue shock syndrome: are they tumour necrosis factor-mediated disorders?

Cited by 45 publications

References 23 publications

Role of Dendritic Cells in Antibody-Dependent Enhancement of Dengue Virus Infection

Role of Dendritic Cells in Antibody-Dependent Enhancement of Dengue Virus Infection

Suppression of lipopolysaccharide-induced antiviral transcription factor (STAT-1 and NF-κB) complexes by antibody-dependent enhancement of macrophage infection by Ross River virus

Dengue Virus Infection of Mast Cells Triggers Endothelial Cell Activation

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