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

Blood ◽  
2013 ◽  
Vol 122 (20) ◽  
pp. 3405-3414 ◽  
Author(s):  
Eugenio D. Hottz ◽  
Juliana F. Lopes ◽  
Carla Freitas ◽  
Rogério Valls-de-Souza ◽  
Marcus F. Oliveira ◽  
...  

Key Points 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-1β.

Blood ◽  
2013 ◽  
Vol 121 (1) ◽  
pp. 95-106 ◽  
Author(s):  
Ming-Fang Wu ◽  
Szu-Ting Chen ◽  
An-Hang Yang ◽  
Wan-Wan Lin ◽  
Yi-Ling Lin ◽  
...  

AbstractPersistent high fever is one of the most typical clinical symptoms in dengue virus (DV)–infected patients. However, the source of endogenous pyrogen (eg, IL-1β) and the signaling cascade leading to the activation of inflammasome and caspase-1, which are essential for IL-1β and IL-18 secretion, during dengue infection have not been elucidated yet. Macrophages can be polarized into distinct phenotypes under the influence of GM-CSF or M-CSF, denoted as GM-Mφ and M-Mφ, respectively. We found that DV induced high levels of IL-1β and IL-18 from GM-Mφ (inflammatory macrophage) and caused cell death (pyroptosis), whereas M-Mφ (resting macrophage) did not produce IL-1β and IL-18 on DV infection even with lipopolysaccharide priming. This observation demonstrates the distinct responses of GM-Mφ and M-Mφ to DV infection. Moreover, up-regulation of pro-IL-1β, pro-IL-18, and NLRP3 associated with caspase-1 activation was observed in DV-infected GM-Mφ, whereas blockade of CLEC5A/MDL-1, a C-type lectin critical for dengue hemorrhagic fever and Japanese encephalitis virus infection, inhibits NLRP3 inflammasome activation and pyrotopsis in GM-Mφ. Thus, DV can activate NLRP3 inflammasome via CLEC5A, and GM-Mφ plays a more important role than M-Mφ in the pathogenesis of DV infection.


2019 ◽  
Vol 93 (21) ◽  
Author(s):  
Pan Pan ◽  
Qi Zhang ◽  
Weiyong Liu ◽  
Wenbiao Wang ◽  
Zizhao Lao ◽  
...  

ABSTRACT Dengue virus (DENV) infection causes serious clinical symptoms, including dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Vascular permeability change is the main feature of the diseases, and the abnormal expression of proinflammatory cytokines is the important cause of vascular permeability change. However, the mechanism underlying vascular permeability induced by DENV has not been fully elucidated. Here, we reveal a distinct mechanism by which DENV infection promotes NLRP3 inflammasome activation and interleukin-1 beta (IL-1β) release to induce endothelial permeability and vascular leakage in mice. DENV M protein interacts with NLRP3 to facilitate NLRP3 inflammasome assembly and activation, which induce proinflammatory cytokine IL-1β activation and release. Notably, M can induce vascular leakage in mouse tissues by activating the NLRP3 inflammasome and IL-1β. More importantly, inflammatory cell infiltration and tissue injuries are induced by M in wild-type (WT) mouse tissues, but they are not affected by M in NLRP3 knockout (NLRP3−/−) mouse tissues. Evans blue intensities in WT mouse tissues are significantly higher than in NLRP3−/− mouse tissues, demonstrating an essential role of NLRP3 in M-induced vascular leakages in mice. Therefore, we propose that upon DENV infection, M interacts with NLRP3 to facilitate inflammasome activation and IL-1β secretion, which lead to the induction of endothelial permeability and vascular leakage in mouse tissues. The important role of the DENV-M-NLRP3-IL-1β axis in the induction of vascular leakage provides new insights into the mechanisms underlying DENV pathogenesis and DENV-associated DHF and DSS development. IMPORTANCE Dengue virus (DENV) is a mosquito-borne pathogen, and infections by this virus are prevalent in over 100 tropical and subtropical countries or regions, with approximately 2.5 billion people at risk. DENV infection induces a spectrum of clinical symptoms, ranging from classical dengue fever (DF) to severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Therefore, it is important to understand the mechanisms underlying DENV pathogenesis. In this study, we reveal that the DENV membrane protein (M) interacts with the host NLRP3 protein to promote NLRP3 inflammasome activation, which leads to the activation and release of a proinflammatory cytokine, interleukin-1 beta (IL-1β). More importantly, we demonstrate that M protein can induce vascular permeability and vascular leakage and that NLRP3 is required for M-induced vascular leakage in mouse tissues. Collectively, this study reveals a distinct mechanism underlying DENV pathogeneses and provides new insights into the development of therapeutic agents for DENV-associated diseases.


2018 ◽  
Vol 17 (4) ◽  
pp. 669-673
Author(s):  
Mahmuda Siddiqua ◽  
Ahmed Nawsher Alam ◽  
AKM Muraduzzaman ◽  
Tahmina Shirin

Introduction: Detection of dengue virus infection as soon as possible is critical for management of dengue virus infected patients. Immuno-chromatographic (ICT) tests are easy, cost effective method for dengue virus antigen detection.The sensitivity and specificity of ICT should compare with a gold standard test like RT-PCR. Aim of this study was to compare two test methods (ICT and RT-PCR), observe dengue serotype and seasonal impact on dengue infection.Methodology & result: The patients of Ibn Sina Medical College Hospital from October 2015 to October 2017 were tested for dengue NS1 antigen by ICT method. Out of 3201 sample tested 32.39% were found positive and 89 of which were re-tested for RT-PCR for comparison. Eighty eight of 89 NS1 positive cases showed positive by RT-PCR method giving an accuracy of 98.87%. Among the RT-PCR positive cases 45 were further analyzed for serotype. DEN-1, DEN-2 or both DEN- 1 and DEN-2 were found in 21, 23 and 1cases respectively. No cases of DEN-3 or DEN-4 were detected.Conclusion: This study showed that easily available and cost effective dengue NS1 antigen detection method (ICT) is as effective as molecular test (RT-PCR). DEN-1 and DEN-2 serotype were prevalent during last few years in Bangladesh. Continuous monitoring of dengue virus serotype is important for prevention and control of sudden epidemic by other serotype. Alert to be more during post monsoon when the peak of dengue virus infection was observed.Bangladesh Journal of Medical Science Vol.17(4) 2018 p.669-673


2016 ◽  
Vol 78 (5-3) ◽  
Author(s):  
Napadol Sudsom ◽  
Suwich Thammapalo ◽  
Theerakamol Pengsakul ◽  
Kuaanan Techato

This study aims to demonstrate a spatial clustering approach for identifying risk households of dengue virus infection during the period of insecticide spraying-ultra low volume (ULV). All households located within 100 m radius of spraying area were recorded with geographic coordinates and divide into three groups of spraying (unsprayed, only outdoor and indoor plus outdoor sprayed house). A total of 45 households with geographic coordinates, were randomly selected to monitor ovitrap index, the percentage of positive ovitraps and the number of eggs per trap, in pre- and post-ULV spraying. Application of spatial analyst tools and spatial statistics tools in ArcGIS 10.1 were used to determine mosquito density and identify risk households using ovitrap index. The prediction maps of Aedes aegypti vector abundance were illustrated by kriging technique. Base on the results, the cluster of Ae. aegypti populations were detected on four day after the spraying. This finding shows the significant spatial pattern of dengue vector populations which may cause high risk areas of dengue virus infection after insecticide treatment. This methodological framework could be used for improving the strategy of dengue vector and outbreak control. The spatial association between dengue vector and the coverage of space spraying requires further study.


2016 ◽  
Vol 47 (3) ◽  
pp. 253-255 ◽  
Author(s):  
MV Krithika ◽  
Prakash Amboiram ◽  
Sneha M Latha ◽  
Binu Ninan ◽  
Febe Renjitha Suman ◽  
...  

We report the first case of haemophagocytic lymphohistiocytosis (HLH) in a neonate secondary to primary Dengue virus infection. This neonate presented in the third week of life with fever, shock and hepatosplenomegaly and was diagnosed to have Dengue infection by serology and HLH was confirmed on bone marrow.


Blood ◽  
2016 ◽  
Vol 128 (17) ◽  
pp. 2153-2164 ◽  
Author(s):  
Shrey Kohli ◽  
Satish Ranjan ◽  
Juliane Hoffmann ◽  
Muhammed Kashif ◽  
Evelyn A. Daniel ◽  
...  

Key Points EVs cause accumulation of activated maternal platelets within the placenta, resulting in a thromboinflammatory response and PE. Activated maternal platelets cause NLRP3-inflammasome activation in trophoblast cells via ATP release and purinergic signaling.


Author(s):  
Acivrida Mega Charisma ◽  
Elis Anita Farida ◽  
Farida Anwari

Severe dengue virus infection often causes proteinuria through several mechanisms, such as leakage of plasma proteins caused by higher protein filtering in the kidneys. The condition of proteinuria in patients with dengue shock syndrome will affect the management, prognosis, and mortality of patients with dengue virus infection. The objectives of this study were to determine the presence of protein in urine samples in patients in which IgG/IgM dengue was detected, to determine the presence of protein in urine samples in patients without dengue infection, and to determine the relationship between proteinuria in dengue patients and the degree of disease severity. The study was conducted in March-June 2020 at the Clinical Laboratory and Inpatient Clinic of Vita Medika Kepung, Kediri Regency. The method used was the consecutive sampling technique. The minimum sample size was 100 respondents with criteria for suspected dengue infection, onset fever > 4 days, age > 2 years, and no indication of other infectious diseases (blood and urine), divided into two groups, group with positive dengue infection and non-dengue group. The results showed that proteinuria was detected in 26% of respondents, secondary dengue infection and positive serological test of IgG, IgM only IgG were detected in 24 (92.3%) respondents and positive IgG and IgM were found in 2 (7.7%) respondents, this was shown by the p-value = 0.000 in the Chi-Square test with a Prevalence Ratio (PR) value of 11,987. In addition, Chi-Square test results indicated that a higher urine protein/albumin led to more severe disease, with p-value = 0.012 and 0.025 (p <0.05) and PR values of 3.333 and 2.800. The results of this study concluded that there was a close relationship between high levels of protein/albumin in the urine with the degree of disease severity in patients with dengue infection. In addition, an increase in urine protein/albumin levels is always followed by a decrease in serum protein/albumin levels.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S651-S652
Author(s):  
Fernando Rosso ◽  
Ana M Sanz ◽  
Luis Gabriel Parra-Lara ◽  
Pablo A Moncada ◽  
Juan D Vélez ◽  
...  

Abstract Background Dengue fever is the most prevalent arbovirus among humans, its incidence has increased since the re-emergence, and Colombia is a hyperendemic country for this infection. The number of solid-organ transplant (SOT) recipients, at risk of acquiring dengue virus infection, is constantly increasing, and there are few data regarding the clinical course and outcomes of dengue infection among this population. The aim of this study was to describe dengue virus infection in SOT recipients in Cali, Colombia. Methods We present a case series of SOT recipients with dengue virus infection, diagnosed by World Health Organization criteria and a positive NS1 and/or IgM dengue antibodies, which were attended at the FVL from 2001 to 2018. Furthermore, we performed a literature review regarding dengue infection in SOT recipients. Results A total of 20 patients were included: 17 kidney and 3 liver recipients. The median age was 50.5 years (IQR = 31–63.5), 65% were female. The median time from transplant to dengue was 27.6 months (IQR = 3.82–59.12), and 3 patients had the infection in the first month after the transplant. The most common symptoms were fever (95%), myalgia, headache, and abdominal pain. Warning signs were present in 75% of patients, thrombocytopenia and hemorrhagic manifestations were present in 30% and 15%, respectively. 35% of patients were classified as severe dengue, and 45% were managed at the intensive care unit. Regarding laboratory findings, six patients had transaminases elevation more than three times the upper limit and 7 had serum creatinine elevation, which returned to normal levels. All patients were discharged and none of them had alterations in the graft function. To date, there are approximately 180 reported cases of dengue in SOT recipients (Table 2). Conclusion Dengue represents a threat among SOT recipients. Unlike other reports, all patients in this series had a full recovery after the infection, suggesting that timely and effective management of patients and the access to high complexity services could prevent fatal cases. Disclosures All authors: No reported disclosures.


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