Antiretroviral therapy partially improves the abnormalities of dendritic cells and lymphoid and myeloid regulatory populations in recently infected HIV patients

Mercedes Márquez-Coello,Francisca Guerrero Sánchez,Clotilde Fernández-Gutiérrez del Álamo,José A. Girón-González,Andrés Martín-Aspas,Montserrat Montes de Oca Arjona

doi:10.1038/s41598-019-48185-2

Abstract

This study aimed to evaluate the effects of antiretroviral therapy on plasmacytoid (pDC) and myeloid (mDC) dendritic cells as well as regulatory T (Treg) and myeloid-derived suppressor (MDSC) cells in HIV-infected patients. Forty-five HIV-infected patients (20 of them with detectable HIV load −10 recently infected and 10 chronically infected patients-, at baseline and after antiretroviral therapy, and 25 with undetectable viral loads) and 20 healthy controls were studied. The influence of HIV load, bacterial translocation (measured by 16S rDNA and lipopolysaccharide-binding protein) and immune activation markers (interleukin –IL- 6, soluble CD14, activated T cells) was analyzed. The absolute numbers and percentages of pDC and mDC were significantly increased in patients. Patients with detectable viral load exhibited increased intracellular expression of IL-12 by mDCs and interferon -IFN- α by pDCs. Activated population markers were elevated, and the proportion of Tregs was significantly higher in HIV-infected patients. The MDSC percentage was similar in patients and controls, but the intracellular expression of IL-10 was significantly higher in patients. The achievement of undetectable HIV load after therapy did not modify bacterial translocation parameters, but induce an increase in pDCs, mDCs and MDSCs only in recently infected patients. Our data support the importance of early antiretroviral therapy to preserve dendritic and regulatory cell function in HIV-infected individuals.

Highlights

Viral and bacterial infections are initially recognized by specialized antigen-presenting cells, including dendritic cells (DCs), which can be classified into two groups: plasmacytoid dendritic cells and myeloid dendritic cells
We have hypothesized that the changes in number or proportions of immune cells detected at baseline were due to the combined effect of human immunodeficiency virus (HIV) itself and microbial translocation-derived products
Consistent with previous data[14,15], we observed that microbial translocation, monocyte and lymphocyte activation persist after antiretroviral therapy (ART)

Summary

Introduction

Viral and bacterial infections are initially recognized by specialized antigen-presenting cells, including dendritic cells (DCs), which can be classified into two groups: plasmacytoid dendritic cells (pDCs) and myeloid dendritic cells (mDCs). MDCs are not significantly reduced in subjects with acute HIV infection[8], a decrease is observed during the chronic phase[9], mainly in those with a lower CD4 T cell count[10]. These data are opposite to the anticipated strong innate immune response after the recognition of viral antigens in other diseases[1,2]. A massive depletion of CD4+ T cells from gut-associated lymphoid tissues occurs and persists during the chronic stage[14,15]. We previously reported that the proportion of Tregs is increased in HIV-infected patients with uncontrolled HIV replication[18]

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