TY - JOUR
T1 - Dengue Virus Serotype-2 Interferes with the Formation of Neutrophil Extracellular Traps
AU - Moreno-Altamirano, Maria Maximina B.
AU - Rodríguez-Espinosa, Oscar
AU - Rojas-Espinosa, Oscar
AU - Pliego-Rivero, Bernardo
AU - Sánchez-Garciá, Francisco J.
N1 - Publisher Copyright:
© 2015 S. Karger AG, Basel.
PY - 2015/11/11
Y1 - 2015/11/11
N2 - Objectives: 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. Conclusion: Our results suggest that DENV-2 inhibits glucose uptake as a metabolism-based way to avoid the formation of NETs.
AB - Objectives: 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. Conclusion: Our results suggest that DENV-2 inhibits glucose uptake as a metabolism-based way to avoid the formation of NETs.
KW - Dengue virus
KW - Neutrophil extracellular traps
KW - Neutrophils
UR - http://www.scopus.com/inward/record.url?scp=84945115024&partnerID=8YFLogxK
U2 - 10.1159/000440723
DO - 10.1159/000440723
M3 - Artículo
C2 - 26496355
AN - SCOPUS:84945115024
SN - 0300-5526
VL - 58
SP - 250
EP - 259
JO - Intervirology
JF - Intervirology
IS - 4
ER -