Revista de SIDA e investigación clínica

Antimicrobial Peptides in Cervicovaginal Lavage of Women Married to HIV Sero-Reactive Men are not Associated with Resistance to HIV but Modulate Mucosal Pro-Inflammatory Response

Abstract

Asim Biswas, Atri Ta, Aritra Das, Samiran Panda and Santasabuj Das

Objectives: It is critical to understand the HIV transmission dynamics in women, who are married to HIV seropositive men and either go into HIV concordant relationship (WCR) or remain HIV discordant (WDR) over a period of time. Antimicrobial peptides (AMPs) are known to possess anti-HIV activities and may offer protection against acquisition of HIV. We investigated if AMP expression is associated with HIV sero-negative status of the WDR population, and how the co-regulated innate immune responses at the genital mucosa differ between WDR and WCR individuals in eastern-India.

Methods: Levels of human beta-defensins, human neutrophil peptides 1-3 and IL-8 were measured by ELISA in the cervicovaginal lavarge (CVL) collected from WCR and WDR individuals. Moreover, we studied the activation of TLR signalling pathways and TNF-alpha induction in THP-1 cells by the microbial components of CVLs and their modulation by pre-treatment of the cells with recombinant AMPs.

Results: Antimicrobial peptide expression in the CVLs showed no significant association with resistance to HIV infection. We observed a shift toward significant co-regulated expression of hBD2 and hBD3 (r=0.52, p<0.0001) and hBD3 and IL-8 (r=-0.26, p=0.03) in the WCR group compared with the WDR (r=0.30, p=0.13 for hBD2 and hBD3; r=-0.15, p=0.44 for hBD3 and IL-8) population. We also found that hBD3 inhibited the pro-inflammatory immune responses induced by CVL, perhaps through the inhibition of TLR4 and TLR1/2 signalling. This was in agreement with the negative correlation between hBD3 and IL-8 expression in the WCR population.

Conclusions: Previous studies identified different microbial composition of CVLs between women living with and without HIV. This might result in a difference in the co-regulated expression of AMPs and inflammatory mediators between the WCR and WDR populations. hBD3 may be critical to control inflammation at the cervico-vaginal mucosa, indicating its novel therapeutic potential in HIV infection.