Dengue virus-activated platelets modulate monocyte immunometabolic response through lipid droplet biogenesis and cytokine signaling
| Autor: | Fernando A. Bozza, Eugenio D. Hottz, Edson F. Assis, Giselle Barbosa-Lima, Guy A. Zimmerman, Sally Liechocki, Thiago Moreno L. Souza, Patrícia T. Bozza |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Blood Platelets Male medicine.medical_treatment Immunology Dengue virus Biology CCL2 medicine.disease_cause Monocytes Dengue 03 medical and health sciences 0302 clinical medicine Immune system Lipid droplet medicine Immunology and Allergy Humans Platelet activation Innate immune system Monocyte Cell Biology Lipid Droplets Dengue Virus Cell biology 030104 developmental biology Cytokine medicine.anatomical_structure 030220 oncology & carcinogenesis Cytokines Female Signal Transduction |
| Zdroj: | Journal of leukocyte biologyREFERENCES. 108(4) |
| ISSN: | 1938-3673 |
| Popis: | Dengue is characterized as one of the most important arthropod-borne human viral diseases, representing a public health problem. Increased activation of immune cells is involved in the progression of infection to severe forms. Recently, our group demonstrated the contribution of platelet–monocyte interaction to inflammatory responses in dengue, adding to evolving evidence that platelets have inflammatory functions and can regulate different aspects of innate immune responses. Furthermore, stimuli-specific-activated platelets can promote phenotypic changes and metabolic reprogramming in monocytes. Thus, this study aimed to evaluate the roles of dengue virus (DENV)-activated platelets on immunometabolic reprogramming of monocytes in vitro, focusing on lipid droplet (LD) biogenesis. We demonstrated that platelets exposed to DENV in vitro form aggregates with monocytes and signal to LD formation and CXCL8/IL-8, IL-10, CCL2, and PGE2 secretion. Pharmacologic inhibition of LD biogenesis prevents PGE2 secretion, but not CXCL8/IL-8 release, by platelet–monocyte complexes. In exploring the mechanisms involved, we demonstrated that LD formation in monocytes exposed to DENV-activated platelets is partially dependent on platelet-produced MIF. Additionally, LD formation is higher in monocytes, which have platelets adhered on their surface, suggesting that beyond paracrine signaling, platelet adhesion is an important event in platelet-mediated modulation of lipid metabolism in monocytes. Together, our results demonstrate that activated platelets aggregate with monocytes during DENV infection and signal to LD biogenesis and the secretion of inflammatory mediators, which may contribute to dengue immunopathogenesis. |
| Databáze: | OpenAIRE |
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