AUTHOR=Rosado-Sánchez Isaac , De Pablo-Bernal Rebeca , Rull Anna , Gónzalez Juan , Moreno Santiago , Vinuesa David , Estrada Vicente , Muñoz-Fernández María Ángeles , Vidal Francesc , Leal Manuel , Pacheco Yolanda María TITLE=Increased Frequencies of Myeloid-Derived Suppressor Cells Precede Immunodiscordance in HIV-Infected Subjects JOURNAL=Frontiers in Immunology VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.581307 DOI=10.3389/fimmu.2020.581307 ISSN=1664-3224 ABSTRACT=Background

We have previously observed increased levels of inflammatory biomarkers and Th17 as well as Treg cells, but not other T-cell specific alterations, preceding immunodiscordance of successfully-treated HIV-infected subjects. Our hypothesis is that this could be related with potential alterations in myeloid-derived suppressor cells (MDSCs) and/or monocyte subsets.

Methods

We determined the frequencies of MDSCs and monocyte subsets and the expression of several functional markers (CCR2, β7-integrin, IDO, PDL1, CD11b) in HIV-infected subjects before treatment. We additionally analyzed follow-up samples after 24 months of suppressive cART in a subgroup of subjects. Bivariate regressions were performed, and correlations with soluble proinflammatory and bacterial translocation biomarkers, as well as with Th17/Treg ratio and anti-CMV titers were explored.

Results

Increased frequencies of MDSCs, but normal distribution of monocyte subsets, preceded immunodiscordance. The expression of several functional markers, such as CCR2, CD16, CD11b and PDL1, on MDSCs and monocyte subsets was altered in this scenario. MDSC and monocyte-related functional markers were associated with soluble biomarkers and T-cell parameters. Several of these cellular alterations were not restored after 24 months of suppressive cART.

Conclusion

An early immunosuppressive environment, characterized by the expansion of MDSCs and Tregs, precedes immunodiscordance and is related with a highly inflammatory status.