Mucosal immunity: A tale of two tissues

HIV monitoring focuses on plasma RNA viral loads and CD4 T- cell counts from the blood, but this only represents a part of the total infection in other parts of the body such as the gut and genital tract. A better understanding of mucosal immunity at these sites has implications for both prevention (microbicides) and treatment research (immune reconstitution outside of PBMCs).

Laura Romas from the University of Manitoba, Canada presented data on the rectal mucosa from HIV-exposed seronegative (HESN) partners in discordant MSM couples and susceptibility to HIV-1 infection, the first time this has been investigated. She found 25 differentially expressed proteins (of 289 identified) that were overabundant in HESN MSM (p< 0.05), and had functions related to acute phase response, antimicrobial defence and Ig-mediated immunity. These proteins did not show a significant correlation (p>0.05) with clinical variables (frequency oral/anal sex, HIV-neutralizing IgA, and viral load of HIV+ partner). One in particular, Antiprotease 1 (AP1) reduced HIV infection by 50% in PBMC culture at physiologically relevant concentrations. Planned further research will aim to elucidate if increased AP1 expression is as a result of HIV-exposure or genetic variability. This could have very interesting implications for MSM prevention strategies and microbicide development.

The GI tract is know as an early site of viral replication and associated immunopathogenesis. Whilst ART stimulates CD4 T – cell recovery in blood, its effects on the GI tract are much less pronounced. However, as earlier initiation of ART seems to preserve more peripheral CD4 T – cells, Claire Deleage from the USA investigated the effect of early ART initiation on the GI tract (lamina propria CD4 T-cells) with a small cohort of Thai patients treated during Fiebig stage 1/2 or 3+ versus chronic controls. Unfortunately, there was no significant recovery of CD4 T-cells in the lamina propria after treatment initiation. After 6 months of HAART all acutely infected treated patients had significant depleted lamina propria CD4 T-cells that persisted through 24 months of treatment. Markers of GI damage, inflammation and immune activation returned to baseline levels after 6 months of ART following an increase during acute HIV-1 infection (day 0). Despite the positive effect of early ART initiation on GI damage markers, the stark lack of CD4 T-cell recovery is disappointing. Fully understanding the complexities of HIV infection in GI tract remains a great challenge, but it is essential if strategies to promote CD4 T-cell recovery in gut are ever to materialise.