Dengue Virus Serotype-2 Interferes with the Formation of Neutrophil Extracellular Traps.
OBJECTIVE
Neutrophils play an important role in the control of pathogens through several mechanisms, including phagocytosis and the formation of neutrophil extracellular traps (NETs). The latter consists of DNA as a backbone with embedded antimicrobial peptides, histones, and proteases, providing a matrix to entrap and in some cases to kill microbes. Some metabolic requirements for NET formation have recently been described. The virus-induced formation of NETs and the role of these traps in viral infections remain scarcely reported. Here, we analyzed whether dengue virus serotype-2 (DENV-2) induces NET formation and the DENV-2 effect on phorbol myristate acetate (PMA)-induced NETs.


METHODS
Peripheral blood-derived neutrophils were exposed in vitro to DENV-2 or exposed to DENV-2 and then stimulated with PMA. NET formation was assessed by fluorescence microscopy. Cell membrane Glut-1, glucose uptake, and reactive oxygen species (ROS) production were assessed.


RESULTS
DENV-2 does not induce the formation of NETs. Moreover, DENV-2 inhibits PMA-induced formation of NETs by about 80%. This effect is not related to the production of ROS. The mechanism seemingly accountable for this inhibitory effect is the DENV-2-mediated inhibition of PMA-induced glucose uptake by neutrophils.


CONCLUSIONS
Our results suggest that DENV-2 inhibits glucose uptake as a metabolism-based way to avoid the formation of NETs.
Laboratorio de Inmunorregulacix00F3;n, Departamento de Inmunologx00ED;a, Escuela Nacional de Ciencias Biolx00F3;gicas, Instituto Politx00E9;cnico Nacional, Mexico City, Mexico.
Maria Maximina B
MM
Moreno-Altamirano
Oscar
O
Rodríguez-Espinosa
Oscar
O
Rojas-Espinosa
Bernardo
B
Pliego-Rivero
Francisco J
FJ
Sánchez-García
D003716:Dengue Virus / Q000276:immunology / Q000378:metabolism*; D065206:Extracellular Traps / Q000276:immunology / Q000821:virology*; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000235:genetics; D008856:Microscopy, Fluorescence; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000648:ultrastructure / Q000821:virology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D065288:Serogroup; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D051272:Glucose Transporter Type 1; D017382:Reactive Oxygen Species; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate