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

Eugenio D. Hottz, Juliana F. Lopes, Carla Freitas, Rogério Valls-de-Souza, Marcus F. Oliveira, Marcelo T. Bozza, Andrea T. Da Poian, Andrew S. Weyrich, Guy A. Zimmerman, Fernando A. Bozza and Patricia T. Bozza.

Blood. 2013;122(20):3405-3414

Speaker: Ko-Lun, Yen (顏克倫)              Time: 15:00~16:00, Nov, 26, 2014

Commentator: Trai-Ming Yeh (葉才明 老師)   Place: Room 601

Abstract:

    Dengue is a tropical infectious disease which is spread by the mosquito Aedes aegypti. There has been a worldwide increasing gepgraphic expansion and the World Health Organization (WHO) considers half the world at risk for infection. There are currently no licensed vaccine or specific therapeutics that can stop its rapid emergence and global spread¹. Dengue virus (DENV) infection is a systemic and dynamic disease. It has a wide clinical spectrum that includes both mild and severe clinical manifestations. Severe dengue (previously known as dengue hemorrhagic fever) is characterized by severe bleeding, thrombocytopenia, vascular permeability with plasma leakage and shock, and severe organ impairment. Thrombocytopenia is commonly observed in mild and severe dengue syndromes and correlates with clinical outcome, it may associate with platelet dysfunction (platelet activation and aggregation) or intravascular coagulation causes hemorrhage. Interleukin-1b (IL-1b) is also known as an important proinflammatory cytokine which has been shown increase in dengue patients, and it has been linked to increased endothelial permeability², thrombosis, and dysregulated in dengue. In this study, author investigated the contribution between endothelium permeability and interleukin-1b (IL-1b) synthesis, processing, and secretion in platelets during dengue virus infection. They observed the propagation of IL-1b and IL-1b-rich microparticles either in dengue patients or platelets exposure to DV in vitro. They also proved the assembly of nucleotide-binding domain leucine rich repeat containing protein (NLRP3) inflammasomes, caspase-1 activation and the secretion of caspase-1 dependent IL-1b in DV infection. Authors investigation indicated the mechanism that platelet-derives IL-1b is chiefly released in microparticles via mitochondrial ROS-triggered NLRP3 inflammasomes activation. In summary,author provide new evidence that DV-triggered platelets shedding of IL-1b-containing microparticles, which likely contribute to the increased vascular permeability and hemoconcentration during dengue infection.

Reference:

1.     World Health Organization. Dengue: guidelines for diagnosis, treatment, prevention and control. WHO Press. 2009.

2.     Bozza FA, Cruz OG, Zagne SM, et al. Multiplex cytokine profile from dengue patients: MIP-1beta and IFN-gamma as predictive factors for severity. BMC infect Dis. 2008;8:86.