Lipopolysaccharide levels are elevated in dengue virus infected patients and correlate with disease severity

Weg, Cornelia A. M. van de; Koraka, Penelope; Gorp, Eric C. M. Van; Mairuhu, Albert T.A.; Supriatna, Mohamad; Soemantri, Augustinus; Vijver, David van de; Osterhaus, Albert D. M. E.; Martina, Benedict

doi:10.1016/j.jcv.2011.09.028

Cited by 52 publications

(47 citation statements)

References 17 publications

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“…49 Therefore, increased an DV-IgG immunocomplex in secondary infection might potentially amplify platelet IL-1b synthesis. It is also possible that increased LPS levels in patients with dengue 50 contribute to activation of IL-1b synthesis and shedding of IL-1b-containing MPs in platelets. 20 In summary, we report increased accumulation of IL-1b in platelets and platelet-derived MPs from patients with dengue and synthesis of IL-1b in platelets activated by DV in vitro.…”

Section: Discussionmentioning

confidence: 99%

Platelets mediate increased endothelium permeability in dengue through NLRP3-inflammasome activation

Hottz

Lopes

Freitas

et al. 2013

Blood

290

380

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• Dengue infection triggers functional inflammasome assembly in platelets.• Platelets may contribute to increased vascular permeability in dengue virus infection by synthesis and release of IL-1b.Dengue is the most frequent hemorrhagic viral disease and re-emergent infection in the world. Although thrombocytopenia is characteristically observed in mild and severe forms of dengue, the role of platelet activation in dengue pathogenesis has not been fully elucidated. We hypothesize that platelets have major roles in inflammatory amplification and increased vascular permeability during severe forms of dengue. Here we investigate interleukin (IL)-1b synthesis, processing, and secretion in platelets during dengue virus (DV) infection and potential contribution of these events to endothelial permeability during infection. We observed increased expression of IL-1b in platelets and plateletderived microparticles from patients with dengue or after platelet exposure to DV in vitro. We demonstrated that DV infection leads to assembly of nucleotide-binding domain leucine rich repeat containing protein (NLRP3) inflammasomes, activation of caspase-1, and caspase-1-dependent IL-1b secretion. Our findings also indicate that plateletderived IL-1b is chiefly released in microparticles through mechanisms dependent on mitochondrial reactive oxygen speciestriggered NLRP3 inflammasomes. Inflammasome activation and platelet shedding of IL-1b-rich microparticles correlated with signs of increased vascular permeability. Moreover, microparticles from DV-stimulated platelets induced enhanced permeability in vitro in an IL-1-dependent manner. Our findings provide new evidence that platelets contribute to increased vascular permeability in DV infection by inflammasome-dependent release of IL-1b. (Blood. 2013;122(20):3405-3414)

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Section: Discussionmentioning

confidence: 99%

Platelets mediate increased endothelium permeability in dengue through NLRP3-inflammasome activation

Hottz

Lopes

Freitas

et al. 2013

Blood

290

380

View full text Add to dashboard Cite

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“…Biomarkers were broadly chosen from three pathways implicated in dengue pathogenesis: (i) inflammation [monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory proteins-1b (MIP-1b), CXCL6, CXCL8, IP-10, CX3CL1, sCD25, granzyme B, IFN-γ, IL-10, hepatocyte growth factor (HGF), soluble (s)CD163, IL-18, RANTES and macrophage migration inhibitory factor (MIF)] [17–22], (ii) endothelial activation [vascular endothelial growth factor (VEGF), intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1)] [23, 24] and (iii) microbial translocation [sCD14 and lipopolysaccharide binding protein (LBP)] [25, 26]. …”

Section: Methodsmentioning

confidence: 99%

Aberrant monocyte responses predict and characterize dengue virus infection in individuals with severe disease

et al. 2017

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BackgroundCurrently, several assays can diagnose acute dengue infection. However, none of these assays can predict the severity of the disease. Biomarkers that predicts the likelihood that a dengue patient will develop a severe form of the disease could permit more efficient patient triage and allows better supportive care for the individual in need, especially during dengue outbreaks.MethodsWe measured 20 plasma markers i.e. IFN-γ, IL-10, granzyme-B, CX3CL1, IP-10, RANTES, CXCL8, CXCL6, VCAM, ICAM, VEGF, HGF, sCD25, IL-18, LBP, sCD14, sCD163, MIF, MCP-1 and MIP-1β in 141 dengue patients in over 230 specimens and correlate the levels of these plasma markers with the development of dengue without warning signs (DWS−), dengue with warning signs (DWS+) and severe dengue (SD).ResultsOur results show that the elevation of plasma levels of IL-18 at both febrile and defervescence phase was significantly associated with DWS+ and SD; whilst increase of sCD14 and LBP at febrile phase were associated with severity of dengue disease. By using receiver operating characteristic (ROC) analysis, the IL-18, LBP and sCD14 were significantly predicted the development of more severe form of dengue disease (DWS+/SD) (AUC = 0.768, P < 0.0001; AUC = 0.819, P < 0.0001 and AUC = 0.647, P = 0.014 respectively). Furthermore, we also found that the levels of VEGF were directly correlated and sCD14 was inversely correlated with platelet count, suggesting that the endothelial activation and microbial translocation may played a role in pathogenesis of dengue disease.ConclusionsGiven that the elevation IL-18, LBP and sCD14 among patients with severe form of dengue disease, our findings suggest a pathogenic role for an aberrant inflammasome and monocyte activation in the development of severe form of dengue disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-017-1226-4) contains supplementary material, which is available to authorized users.

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“…Hence, this could possibly explain the failure to differentiate between non-dengue fever and dengue without warning signs in our study. Another possible explanation is that neopterin is only elevated during the plasma leakage which is seen in dengue with warning signs [23].…”

Section: Discussionmentioning

confidence: 99%

Biomarkers in differentiating clinical dengue cases: A prospective cohort study

Kim¹,

Low²,

Gan³

et al. 2015

J Coast Life Med

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Lipopolysaccharide levels are elevated in dengue virus infected patients and correlate with disease severity

Abstract: In this study we show evidence of elevated LPS levels during DENV infection. Moreover, a correlation between LPS levels and disease severity was found, especially when disease severity was determined in terms of plasma leakage.

Cited by 52 publications

References 17 publications

Platelets mediate increased endothelium permeability in dengue through NLRP3-inflammasome activation

Platelets mediate increased endothelium permeability in dengue through NLRP3-inflammasome activation

Aberrant monocyte responses predict and characterize dengue virus infection in individuals with severe disease

Biomarkers in differentiating clinical dengue cases: A prospective cohort study

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