Levels of innate immune factors in genital fluids: association of alpha defensins and LL-37 with genital infections and increased HIV acquisition.
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.
Levinson
Pauline
P
Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Solna, Stockholm, Sweden.
Kaul
Rupert
R
Kimani
Joshua
J
Ngugi
Elizabeth
E
Moses
Stephen
S
MacDonald
Kelly S
KS
Broliden
Kristina
K
Hirbod
Taha
T
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
D023181:Antimicrobial Cationic Peptides; D023084:alpha-Defensins; D054804:Cathelicidins