A Re‐evaluation of the Mechanisms Leading to Dengue Hemorrhagic Fever

Noisakran, Sansanee; Chokephaibulkit, Kulkanya; Songprakhon, Pucharee; Onlamoon, Nattawat; Hsiao, Hui Mien; Villinger, François; Ansari, Aftab A.; Perng, Guey Chuen

doi:10.1111/j.1749-6632.2009.05050.x

Cited by 49 publications

(50 citation statements)

References 40 publications

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“…With evidence suggesting platelets can be infected by DENV and become activated [17,18,31], an ex vivo study was carried out to verify the DENV-infected platelets, which could be aggregated with monocytes directly. Platelets were purified and infected with DENV as previously described [8].…”

Section: Resultsmentioning

confidence: 99%

Transient Monocytosis Subjugates Low Platelet Count in Adult Dengue Patients

Tsai

Chang

et al. 2017

Biomed Hub

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Background: Dengue is one of the most important vector-borne human viral diseases globally. The kinetic changes of hematological parameters of dengue in adult Taiwanese patients have seldomly been systematically investigated and characterized. Methodology/Principal Findings: Serial laboratory data of 1,015 adult patients who were diagnosed with dengue virus serotype 2 (DENV2) and 3 (DENV3) infections in southern Taiwan were retrospectively examined. Prominent parameters were verified with specimens from a 2015 dengue outbreak. Higher absolute monocyte counts on day 5 in severe patients than mild fever subjects after the onset of fever was seen. The absolute number of monocytes was significantly greater in those with DENV2 than DENV3 infections in spite of subtle differences in laboratory tests. Platelet counts were lowest and activated partial thromboplastin time was highest on day 5 in patients with severe conditions. In addition, sudden downward platelet counts corresponding to a transient surge of monocytes on day 4 onward was observed. Fluorescence-activated cell sorting analysis of peripheral blood mononuclear cells obtained from acute dengue patients and experimental investigations revealed that phagocytic effects of innate immune cells contribute to thrombocytopenia in dengue patients. Conclusion: Innate phagocytic cells play an essential role in low platelet counts in adult patients with dengue virus infections.

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Section: Resultsmentioning

confidence: 99%

Transient Monocytosis Subjugates Low Platelet Count in Adult Dengue Patients

Tsai

Chang

et al. 2017

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“…our in vitro results confirm DV-triggered IL-1b synthesis by platelets. Whether this is due to outside-in activation of intracellular signaling pathways and/or internalization of DV into platelets 46,47 requires further investigation. We also recognize that other factors including cytokines, antibodies, and coagulation factors may also contribute to platelet activation in dengue.…”

Section: Discussionmentioning

confidence: 99%

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

Hottz

Lopes

Freitas

et al. 2013

Blood

291

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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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“…[107][108][109] It has been suggested that the degree of thrombocytopenia correlates with clinical severity and complement activation. 110 As a result of reduced platelet counts and increased complement activation there is increased vascular fragility and thus an increased risk of haemorrhage.…”

Section: Thrombocytopeniamentioning

confidence: 99%