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Neutrophil Extracellular Traps Effectively Control Acute Chikungunya Virus Infection.
Front Immunol. 2019; 10:3108.FI

Abstract

The Chikungunya virus (CHIKV) is a re-emerging arbovirus, in which its infection causes a febrile illness also commonly associated with severe joint pain and myalgia. Although the immune response to CHIKV has been studied, a better understanding of the virus-host interaction mechanisms may lead to more effective therapeutic interventions. In this context, neutrophil extracellular traps (NETs) have been described as a key mediator involved in the control of many pathogens, including several bacteria and viruses, but no reports of this important protective mechanism were documented during CHIKV infection. Here we demonstrate that the experimental infection of mouse-isolated neutrophils with CHIKV resulted in NETosis (NETs release) through a mechanism dependent on TLR7 activation and reactive oxygen species generation. In vitro, mouse-isolated neutrophils stimulated with phorbol 12-myristate 13-acetate release NETs that once incubated with CHIKV, resulting in further virus capture and neutralization. In vivo, NETs inhibition by the treatment of the mice with DNase resulted in the enhanced susceptibility of IFNAR-/- mice to CHIKV experimental acute infection. Lastly, by accessing the levels of MPO-DNA complex on the acutely CHIKV-infected patients, we found a correlation between the levels of NETs and the viral load in the blood, suggesting that NETs are also released in natural human infection cases. Altogether our findings characterize NETosis as a contributing natural process to control CHIKV acute infection, presenting an antiviral effect that helps to control systemic virus levels.

Authors+Show Affiliations

Department of Pharmacology, School of Medicine of Ribeirao Preto, University of São Paulo, Ribeirao Preto, Brazil.Department of Pharmacology, School of Medicine of Ribeirao Preto, University of São Paulo, Ribeirao Preto, Brazil.Department of Biochemistry and Immunology, School of Medicine of Ribeirao Preto, University of São Paulo, Ribeirao Preto, Brazil.Department of Biochemistry and Immunology, School of Medicine of Ribeirao Preto, University of São Paulo, Ribeirao Preto, Brazil.Virology Research Center, School of Medicine of Ribeirao Preto, University of São Paulo, Ribeirao Preto, Brazil.Virology Research Center, School of Medicine of Ribeirao Preto, University of São Paulo, Ribeirao Preto, Brazil.Department of Virology and Experimental Therapy, Institute Aggeu Magalhaes, Oswaldo Cruz Foundation, Recife, Brazil.Department of Pharmacology, School of Medicine of Ribeirao Preto, University of São Paulo, Ribeirao Preto, Brazil.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32082301

Citation

Hiroki, Carlos H., et al. "Neutrophil Extracellular Traps Effectively Control Acute Chikungunya Virus Infection." Frontiers in Immunology, vol. 10, 2019, p. 3108.
Hiroki CH, Toller-Kawahisa JE, Fumagalli MJ, et al. Neutrophil Extracellular Traps Effectively Control Acute Chikungunya Virus Infection. Front Immunol. 2019;10:3108.
Hiroki, C. H., Toller-Kawahisa, J. E., Fumagalli, M. J., Colon, D. F., Figueiredo, L. T. M., Fonseca, B. A. L. D., Franca, R. F. O., & Cunha, F. Q. (2019). Neutrophil Extracellular Traps Effectively Control Acute Chikungunya Virus Infection. Frontiers in Immunology, 10, 3108. https://doi.org/10.3389/fimmu.2019.03108
Hiroki CH, et al. Neutrophil Extracellular Traps Effectively Control Acute Chikungunya Virus Infection. Front Immunol. 2019;10:3108. PubMed PMID: 32082301.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neutrophil Extracellular Traps Effectively Control Acute Chikungunya Virus Infection. AU - Hiroki,Carlos H, AU - Toller-Kawahisa,Juliana E, AU - Fumagalli,Marcilio J, AU - Colon,David F, AU - Figueiredo,Luiz T M, AU - Fonseca,Bendito A L D, AU - Franca,Rafael F O, AU - Cunha,Fernando Q, Y1 - 2020/01/31/ PY - 2019/06/17/received PY - 2019/12/19/accepted PY - 2020/2/22/entrez PY - 2020/2/23/pubmed PY - 2020/11/18/medline KW - Chikungunya KW - NETs KW - innate response KW - neutrophils KW - viral infection SP - 3108 EP - 3108 JF - Frontiers in immunology JO - Front Immunol VL - 10 N2 - The Chikungunya virus (CHIKV) is a re-emerging arbovirus, in which its infection causes a febrile illness also commonly associated with severe joint pain and myalgia. Although the immune response to CHIKV has been studied, a better understanding of the virus-host interaction mechanisms may lead to more effective therapeutic interventions. In this context, neutrophil extracellular traps (NETs) have been described as a key mediator involved in the control of many pathogens, including several bacteria and viruses, but no reports of this important protective mechanism were documented during CHIKV infection. Here we demonstrate that the experimental infection of mouse-isolated neutrophils with CHIKV resulted in NETosis (NETs release) through a mechanism dependent on TLR7 activation and reactive oxygen species generation. In vitro, mouse-isolated neutrophils stimulated with phorbol 12-myristate 13-acetate release NETs that once incubated with CHIKV, resulting in further virus capture and neutralization. In vivo, NETs inhibition by the treatment of the mice with DNase resulted in the enhanced susceptibility of IFNAR-/- mice to CHIKV experimental acute infection. Lastly, by accessing the levels of MPO-DNA complex on the acutely CHIKV-infected patients, we found a correlation between the levels of NETs and the viral load in the blood, suggesting that NETs are also released in natural human infection cases. Altogether our findings characterize NETosis as a contributing natural process to control CHIKV acute infection, presenting an antiviral effect that helps to control systemic virus levels. SN - 1664-3224 UR - https://www.unboundmedicine.com/medline/citation/32082301/Neutrophil_Extracellular_Traps_Effectively_Control_Acute_Chikungunya_Virus_Infection_ L2 - https://doi.org/10.3389/fimmu.2019.03108 DB - PRIME DP - Unbound Medicine ER -