A View of Platelets in Dengue

Abstract

Platelets were mainly associated with coagulation and hemostasis; however, other biological effects have been attributed to platelets, including angiogenesis, extracellular matrix synthesis, inflammation, and immune response. Dengue virus infection causes 200 million cases of severe flu-like illness annually, escalating to life-threatening hemorrhagic fever or shock syndrome. Some hypotheses are postulated for immunopathogenesis of dengue, including antibody enhancement theory, T-cell activation of cross-reactive memory, and original antigenic sin. All hypotheses, to some extent, induce an overproduction or a skewed profile of cytokine release, giving rise to the term cytokine storm/cytokine tsunami. Although thrombocytopenia is typical of both mild and severe diseases, the mechanism triggering platelet reduction is incompletely understood. In dengue, platelets are one of the major cell populations affected by direct and/or indirect mechanisms of infection. It is common to observe both thrombocytopenia and platelet dysfunction in dengue, both strongly related to the clinical outcome. Thus, platelets are frequently affected in dengue, either for alteration of their own functionality, for "silent transport" of virus, or as an anti-viral immune cell. In this way, we describe some of functional aspects of platelets on dengue, observing circulating mediators, intraplatelet proteins contents, morphology, activation markers, and ability to interact with dengue virus.

Cellular and Molecular Immunology Approaches for the Development of Immunotherapies against the New Coronavirus (SARS-CoV-2): Challenges to Near-Future Breakthroughs

“…With regard to immunological responses, platelets present multiple immune receptors, such as immunoglobulin or complement receptors and Toll-like receptors (TLRs) [85, 94], and the capacity of NRLP-3 inflammasome activation and production of cytokines IL-1β and TGF-β [95][96][97]. These functions are achieved through direct interaction with endothelial cells, as well as monocytes, lymphocytes (plateletleukocyte aggregates (PLA)) and neutrophils (platelet-neutrophil aggregates (PNA)) in a process regulated by Pselectin [93,98,99].…”

Dengue Fever: Therapeutic Potential of Carica papaya L. Leaves

“…Flavonoids isolated from papaya leaves have been reported to inhibit a protease involved in viral assembly (Charan et al, 2016). It has been proposed that dengue virus serotype two can bind to platelets directly to destroy them or can cause their peripheral destruction indirectly by promoting the production of anti-platelet or crossreaction antibodies (da Costa Barros and de-Oliveira-Pinto, 2018). Papaya leaf extract has been reported to cause membrane stabilization, which may facilitate the reversal of peripheral platelet destruction by dengue virus (Ranasinghe et al, 2012).…”

“…The possible role of antioxidant and free radical scavenging properties of papaya leaf extract in aiding the prevention of hemolysis and bleeding have also been suggested (Pandita et al, 2019). However, dengue virus induces the reduction in proliferation of platelets by inhibiting megakaryocytopoiesis or inhibiting differentiation of stem cells into megakaryocyte precursor cells (da Costa Barros and de-Oliveira-Pinto, 2018). Papaya leave extract has been found to increase expression ALOX 12 (Figure 8) gene by 15-fold, which further increases megakaryocyte production and its conversion into platelets as well as the production of platelets through the 12-HETE mediated pathway (McRedmond et al, 2004;Sundarmurthy et al, 2017).…”