Elevated TNF-α Induces Thrombophagocytosis by Mononuclear Cells in ex vivo Whole-Blood CoCulture with Dengue Virus

Rahmat Dani Satria, Ming Kai Jhan, Chia Ling Chen, Po Chun Tseng, Yung Ting Wang, Chiou Feng Lin

Research output: Contribution to journalReview articlepeer-review


Background: 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.

Original languageEnglish
Pages (from-to)1717-1728
Number of pages12
JournalJournal of Inflammation Research
Publication statusPublished - 2022


  • Dengue virus
  • Ex vivo
  • Monocyte
  • Thrombophagocytosis
  • TNF-α

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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