Microbial Translocation Is Linked to a Specific Immune Activation Profile in HIV-1-Infected Adults With Suppressed Viremia.

Mehwish Younas,Corinne Merle,Thierry Vincent,Renaud Cezar,Céline Fernandez,Pascale Fabbro,Robert Sabatier,Lucy Kundura,Claudine Barbuat,Christina Psomas,Audrey Winter,Jacques Reynes,Pierre Corbeau,Olivier Moranne,Vincent Le Moing,Albert Sotto,Pierre Portalès ,Catherine Dunyach-Rémy ,Nadine Atoui ,Christelle Reynès ,Jean‐Philippe Lavigne

doi:10.3389/fimmu.2019.02185

Abstract

Persistent immune activation in virologically suppressed HIV-1 patients, which may be the consequence of various factors including microbial translocation, is a major cause of comorbidities. We have previously shown that different profiles of immune activation may be distinguished in virological responders. Here, we tested the hypothesis that a particular profile might be the consequence of microbial translocation. To this aim, we measured 64 soluble and cell surface markers of inflammation and CD4+ and CD8+ T-cell, B cell, monocyte, NK cell, and endothelial activation in 140 adults under efficient antiretroviral therapy, and classified patients and markers using a double hierarchical clustering analysis. We also measured the plasma levels of the microbial translocation markers bacterial DNA, lipopolysaccharide binding protein (LBP), intestinal-fatty acid binding protein, and soluble CD14. We identified five different immune activation profiles. Patients with an immune activation profile characterized by a high percentage of CD38+CD8+ T-cells and a high level of the endothelial activation marker soluble Thrombomodulin, presented with higher LBP mean (± SEM) concentrations (33.3 ± 1.7 vs. 28.7 ± 0.9 μg/mL, p = 0.025) than patients with other profiles. Our data are consistent with the hypothesis that the immune activation profiles we described are the result of different etiological factors. We propose a model, where particular causes of immune activation, as microbial translocation, drive particular immune activation profiles responsible for particular comorbidities.

Highlights

Immune activation plays a major role during HIV-1 infection
Inflammation was evaluated via soluble Tumor Necrosis Factor receptor type I and C-reactive protein (CRP) concentrations, and endothelium activation was evaluated via soluble Endothelial Protein C Receptor, soluble
We show that adding to this cohort 20 younger individuals with a shorter period of infection and aviremia and a higher CD4 count before antiretroviral therapy (ART), did not disrupt the hierarchical clustering

Summary

Introduction

Immune activation plays a major role during HIV-1 infection. In the short term, it is the main driver of CD4 T-cell loss [1]. It fuels non-AIDS-linked morbidities such as atherothrombosis, osteoporosis, metabolic syndrome, neurocognitive disorders, liver steatosis, kidney failure, frailty, and certain types of cancer, even under antiretroviral therapy (ART) [2]. These diseases are responsible for over 80% of deaths among virologic responders [3]. Using two independent hierarchical clustering analyses, we identified five patient groups characterized by very different immune activation profiles [4] This observation highlights the fact that virological responders do not all present with the same types of immune activation. The level of persistent HIV production is variable among virologic responders

Methods

Results

Conclusion