Journal of Inflammation Research (Mar 2022)
Elevated TNF-α Induces Thrombophagocytosis by Mononuclear Cells in ex vivo Whole-Blood Co-Culture with Dengue Virus
Abstract
Rahmat Dani Satria,1– 4,* Ming-Kai Jhan,4,5,* Chia-Ling Chen,6 Po-Chun Tseng,4,7 Yung-Ting Wang,4 Chiou-Feng Lin4,5,7 1International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei, 110, Taiwan; 2Department of Clinical Pathology and Laboratory Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, 55281, Indonesia; 3Clinical Laboratory Installation, Dr. Sardjito Central General Hospital, Yogyakarta, 55281, Indonesia; 4Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 110, Taiwan; 5Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, 110, Taiwan; 6School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, 110, Taiwan; 7Core Laboratory of Immune Monitoring, Office of Research & Development, Taipei Medical University, Taipei, 110, Taiwan*These authors contributed equally to this workCorrespondence: Chiou-Feng Lin, Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 110, Taiwan, Tel +886 2 27361661 ext. 7156, Email [email protected]: Infection with dengue virus (DENV) causes hematological complications in dengue diseases characterized by thrombocytopenia accompanied by macrophage activation syndrome and hemophagocytosis in fatal patients.Methods: In this study, we investigate the undefined mechanisms underlying the progression of thrombocytopenia caused by thrombophagocytosis based on an ex vivo whole-blood co-culture model of DENV infection for mimicking the acute febrile phase of infection.Results: In this model, complete blood count test showed a decrease in monocytes (p < 0.01), but not neutrophils nor other white blood cells, accompanied by a low thrombocyte count (p < 0.01) in DENV infection with a positive correlation (r = 0.636, p < 0.05). Furthermore, DENV exposure caused significant thrombophagocytosis in mononuclear cells (p < 0.05). Abnormal production of tumor necrosis factor (TNF)-α was highly associated with induction of thrombophagocytosis (r = 0.758, p < 0.01), decreased monocytes (r = − 0.758, p < 0.01), and decreased thrombocyte (r = − 0.728, p < 0.01). Neutralizing TNF-α considerably (p < 0.05) reversed such DENV-induced effects and was further validated by immunostaining-based flow cytometry analysis on mononuclear CD14 positive monocytes. Exogenous administration of TNF-α effectively caused thrombophagocytosis accompanied by decreased monocytes and thrombocytes, probably causing monocyte activation.Conclusion: These results demonstrate the potential pathogenesis of thrombocytopenia caused by TNF-α-induced thrombophagocytosis in monocytes during DENV infection.Graphical Abstract: Keywords: dengue virus, monocyte, thrombophagocytosis, ex vivo, TNF-α
