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

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.

Keywords: bacterial translocation; cell activation; coagulation; endothelium; inflammation.

Figure 1

Identification of the patient's immune activation profiles. Heatmap showing the hierarchical clustering of the activation markers (vertical) and of the patients (horizontal). The five profiles of immune activation issued from the patients clustering (A–E) are indicated.

Figure 2

Characterization of the immune activation profiles (A–E). Differences in the level of various activation markers between each cluster of patients and the other clusters are shown. Microbial translocation in patients and healthy donors (F–K). Plasma levels of rDNA (F), LBP (G), sCD14 (H), and I-FABP (I) are presented as mean values and standard deviation; p-values are shown. Correlations between rDNA and LBP (J), and between sCD14 and I-FABP (K) in patients are shown. Correlations between microbial translocation and immune activation markers in patients (L–Q).

Figure 3

Microbial translocation markers are elevated in patients with immune activation profile D. I-FABP (A) and LBP (B) mean values and standard deviations in patients according to their immune activation profile. p-value of the difference for each microbial translocation marker between Profile D and the other immune activation profiles is indicated. Characterization of the immune activation profile D (C,D). Differences in the percentage of CD8+ T-cells expressing CD57 (C) and in the level of sThrombomodulin (D) between profile D and the other profiles are shown.