title: Levels of innate immune factors in genital fluids: association of alpha defensins and LL-37 with genital infections and increased HIV acquisition.
abstract: BACKGROUND
  Several mucosal innate immune proteins exhibit HIV inhibitory activity and their analogues are potential microbicide candidates. However, their clinical associations and in-vivo role in cervicovaginal host defense against HIV acquisition are poorly defined.
  
  
  METHODS
  Cervicovaginal secretions (CVSs) were collected from HIV uninfected Kenyan sex workers at enrolment into an HIV prevention trial. After trial completion, CVS from participants acquiring HIV (cases) and matched controls were assessed for levels of innate immune factors and HIV neutralizing capacity, by blinded investigators. Cross-sectional and prospective associations of innate immune factors were examined.
  
  
  RESULTS
  CVS contained high levels of defensins (human neutrophil peptide-1-3 and human beta defensin-2-3), LL-37 and secretory leukocyte protease inhibitor. Regulated upon activation normal T-cell expressed and secreted levels were lower, and IFNalpha was undetectable. CVS from 20% of participants neutralized a clade A primary HIV isolate, and 12% neutralized both clade A and C isolates. HIV neutralization was correlated with human neutrophil peptide-1-3 (alpha-defensins) and LL-37 levels. However, alpha-defensin and LL-37 levels were increased in participants with bacterial sexually transmitted infections and were independently associated with increased HIV acquisition in multivariate analysis.
  
  
  CONCLUSIONS
  Despite significant HIV inhibitory activity, cervicovaginal levels of alpha-defensins and LL-37 were associated with increased HIV acquisition, perhaps due to their association with bacterial sexually transmitted infections.
authors.affiliation: Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Solna, Stockholm, Sweden.
authors.forename: Pauline
authors.initials: P
authors.lastname: Levinson
authors.forename: Rupert
authors.initials: R
authors.lastname: Kaul
authors.forename: Joshua
authors.initials: J
authors.lastname: Kimani
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ngugi
authors.forename: Stephen
authors.initials: S
authors.lastname: Moses
authors.forename: Kelly S
authors.initials: KS
authors.lastname: MacDonald
authors.forename: Kristina
authors.initials: K
authors.lastname: Broliden
authors.forename: Taha
authors.initials: T
authors.lastname: Hirbod
mesh_terms: D000293:Adolescent; D000328:Adult; D019072:Antibiotic Prophylaxis; D023181:Antimicrobial Cationic Peptides / Q000032:analysis*; D005122:Exudates and Transudates / Q000276:immunology; D005260:Female; D005836:Genitalia, Female / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control / Q000635:transmission; D006801:Humans; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D008875:Middle Aged; D011446:Prospective Studies; D011477:Sex Work; D015231:Sexually Transmitted Diseases, Bacterial / Q000276:immunology / Q000517:prevention & control / Q000635:transmission; D055815:Young Adult; D023084:alpha-Defensins / Q000032:analysis*; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D023084:alpha-Defensins; D054804:Cathelicidins