Format

Send to

Choose Destination
PLoS One. 2012;7(6):e38100. doi: 10.1371/journal.pone.0038100. Epub 2012 Jun 4.

Selective impact of HIV disease progression on the innate immune system in the human female reproductive tract.

Author information

1
Department of Medicine, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, United States of America. Timothy.Lahey@Dartmouth.edu

Abstract

BACKGROUND:

We have previously demonstrated intrinsic anti-HIV activity in cervicovaginal lavage (CVL) from HIV-infected women with high CD4 counts and not on antiretroviral therapy. However, the impact of HIV disease progression on CVL innate immune responses has not been delineated.

METHODS:

CVL from 57 HIV-infected women not on antiretroviral therapy were collected by washing the cervicovaginal area with 10 ml of sterile normal saline. We characterized subject HIV disease progression by CD4 count strata: >500 cells/µl, 200-500 cells/µl, or <200 cells/µl of blood. To assess CVL anti-HIV activity, we incubated TZM-bl cells with HIV plus or minus CVL. Antimicrobials, cytokines, chemokines and anti-gp160 HIV IgG antibodies were measured by ELISA and Luminex.

RESULTS:

CVL exhibited broad anti-HIV activity against multiple laboratory-adapted and transmitted/founder (T/F) viruses, with anti-HIV activity ranging from 0 to 100% showing wide variation between viral strains. Although there was broad CVL inhibition of most both laboratory-adapted and T/F virus strains, there was practically no inhibition of T/F strain RHPA.c, which was isolated from a woman newly infected via heterosexual intercourse. HIV disease progression, measured by declining CD4 T cell counts, resulted in a selective reduction in intrinsic anti-HIV activity in CVL that paralleled CVL decreases in human beta-defensin 2 and increases in Elafin and secretory leukocyte protease inhibitor. HIV disease progress predicted decreased CVL anti-HIV activity against both laboratory-adapted and T/F strains of HIV. Anti-HIV activity exhibited close associations with CVL levels of fourteen cytokines and chemokines.

CONCLUSIONS:

Amid a multifaceted immune defense against HIV-1 and other sexually transmitted pathogens, HIV disease progression is associated with selective disturbances in both CVL anti-HIV activity and specific innate immune defenses in the human female reproductive tract (FRT). Overall, these studies indicate that innate immune protection in the FRT is compromised as women progress to AIDS.

PMID:
22675510
PMCID:
PMC3366961
DOI:
10.1371/journal.pone.0038100
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

Publication types

MeSH terms

Substances

Grant support

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center