Elevated TNF-α Induces Thrombophagocytosis by Mononuclear Cells in ex vivo Whole-Blood Co-Culture with Dengue Virus.
J Inflamm Res
; 15: 1717-1728, 2022.
Article
en En
| MEDLINE
| ID: mdl-35282270
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
2_ODS3
/
3_ND
Problema de salud:
2_enfermedades_transmissibles
/
3_dengue
/
3_neglected_diseases
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Inflamm Res
Año:
2022
Tipo del documento:
Article
País de afiliación:
Taiwán