title: Neutrophil extracellular traps mediate a host defense response to human immunodeficiency virus-1.
abstract: Neutrophils contribute to pathogen clearance by producing neutrophil extracellular traps (NETs), which are genomic DNA-based net-like structures that capture bacteria and fungi. Although NETs also express antiviral factors, such as myeloperoxidase and α-defensin, the involvement of NETs in antiviral responses remains unclear. We show that NETs capture human immunodeficiency virus (HIV)-1 and promote HIV-1 elimination through myeloperoxidase and α-defensin. Neutrophils detect HIV-1 by Toll-like receptors (TLRs) TLR7 and TLR8, which recognize viral nucleic acids. Engagement of TLR7 and TLR8 induces the generation of reactive oxygen species that trigger NET formation, leading to NET-dependent HIV-1 elimination. However, HIV-1 counteracts this response by inducing C-type lectin CD209-dependent production of interleukin (IL)-10 by dendritic cells to inhibit NET formation. IL-10 suppresses the reactive oxygen species-dependent generation of NETs induced upon TLR7 and TLR8 engagement, resulting in disrupted NET-dependent HIV-1 elimination. Therefore, NET formation is an antiviral response that is counteracted by HIV-1.
authors: Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Suita, Japan.
authors: Tatsuya
authors: T
authors: Saitoh
authors: Jun
authors: J
authors: Komano
authors: Yasunori
authors: Y
authors: Saitoh
authors: Takuma
authors: T
authors: Misawa
authors: Michihiro
authors: M
authors: Takahama
authors: Tatsuya
authors: T
authors: Kozaki
authors: Takuya
authors: T
authors: Uehata
authors: Hidenori
authors: H
authors: Iwasaki
authors: Hiroko
authors: H
authors: Omori
authors: Shoji
authors: S
authors: Yamaoka
authors: Naoki
authors: N
authors: Yamamoto
authors: Shizuo
authors: S
authors: Akira
mesh_terms: D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000821:virology; D005110:Extracellular Space / Q000378:metabolism / Q000821:virology*; D015497:HIV-1 / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism* / Q000821:virology*; D009195:Peroxidase / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D051199:Toll-Like Receptor 7 / Q000378:metabolism; D051200:Toll-Like Receptor 8 / Q000378:metabolism; D023084:alpha-Defensins / Q000378:metabolism; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D016753:Interleukin-10; D037181:Lectins, C-Type; D009195:Peroxidase; D011956:Receptors, Cell Surface; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D023084:alpha-Defensins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C495348:TLR7 protein, human; C495349:TLR8 protein, human