title: Involvement of neutrophil hyporesponse and the role of Toll-like receptors in human immunodeficiency virus 1 protection.
abstract: OBJECTIVE
  Neutrophils contribute to pathogen clearance through pattern recognition receptors (PRRs) activation. However, the role of PRRs in neutrophils in both HIV-1-infected [HIV-1(+)] and HIV-1-exposed seronegative individuals (HESN) is unknown. Here, a study was carried out to evaluate the level of PRR mRNAs and cytokines produced after activation of neutrophils from HIV-1(+), HESN and healthy donors.
  
  
  METHODS
  The neutrophils were stimulated with specific agonists for TLR2, TLR4 and TLR9 in the presence of HIV-1 particles. Pro-inflammatory cytokine production, expression of neutrophil activation markers and reactive oxygen species (ROS) production were analyzed in neutrophils from HESN, HIV-1(+) and healthy donors (controls).
  
  
  RESULTS
  We found that neutrophils from HESN presented reduced expression of PRR mRNAs (TLR4, TLR9, NOD1, NOD2, NLRC4 and RIG-I) and reduced expression of cytokine mRNAs (IL-1β, IL-6, IL-18, TNF-α and TGF-β). Moreover, neutrophils from HESN were less sensitive to stimulation through TLR4. Furthermore, neutrophils from HESN challenged with HIV-1 and stimulated with TLR2 and TLR4 agonists, produced significantly lower levels of reactive oxygen species, versus HIV-1(+).
  
  
  CONCLUSIONS
  A differential pattern of PRR expression and release of innate immune factors in neutrophils from HESN is evident. Our results suggest that lower neutrophil activation can be involved in protection against HIV-1 infection.
authors.affiliation: INFETTARE, Facultad de Medicina, Universidad Cooperativa de Colombia, Medellin, Colombia.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Hernandez
authors.affiliation: Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Giraldo
authors.affiliation: GIMAP EA3064, Faculté de Medicine de Saint Etienne, Université de Lyon, Lyon, France.
authors.forename: Stephane
authors.initials: S
authors.lastname: Paul
authors.affiliation: Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.
authors.forename: Silvio
authors.initials: S
authors.lastname: Urcuqui-Inchima
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D007378:Interleukins / Q000096:biosynthesis / Q000276:immunology; D055666:Lipopeptides / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008233:Lymphotoxin-alpha / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000235:genetics / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000235:genetics / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000819:agonists / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology; D014771:Virion / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; C513201:CpG-B 2006; D007378:Interleukins; D055666:Lipopeptides; D008070:Lipopolysaccharides; D008233:Lymphotoxin-alpha; D009838:Oligodeoxyribonucleotides; C560312:Pam2CSK4 lipopeptide; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C495371:TLR9 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha