Christine Bourgeois

French Institute of Health and Medical Research | Inserm · IMVA-HB Center UMR 1184 Center for Immunology of viral autoimmune hematologic and bacterial diseases

During chronic SIV/HIV infection, adipose tissue (AT) is the target of both antiretroviral treatment (ART) and the virus. AT might subsequently contribute to the low-grade systemic inflammation observed in patients on ART. To evaluate the inflammatory profile of AT during chronic SIV/HIV infection, we assayed subcutaneous and visceral abdominal AT...

Low monocyte (m)HLA-DR expression is associated with mortality in sepsis. G-286A*rs3087456 polymorphism in promoter III of HLA class II transactivator (CIITA), the master regulator of HLA, has been associated with autoimmune diseases but its role in sepsis has never been demonstrated. In 203 patients in septic shock, GG genotype was associated with...

For people living with HIV, treatment with integrase-strand-transfer-inhibitors (INSTIs) can promote adipose tissue (AT) gain. We previously demonstrated that INSTIs can induce hypertrophy and fibrosis in AT of macaques and humans. By promoting energy expenditure, the emergence of beige adipocytes in white AT (beiging) could play an important role...

The well documented association between obesity and the severity of SARS-CoV-2 infection raises the question of whether adipose tissue (AT) is impacted during this infection. Using a model of SARS-CoV-2 infection in cynomolgus macaques, we detected the virus within subcutaneous AT (SCAT) but not in visceral AT (VAT) or epicardial AT on day 7 post-i...

Virus-specific CD8+ T cells play a central role in HIV-1 natural controllers to maintain suppressed viremia in the absence of antiretroviral therapy. These cells display a memory program that confers them stemness properties, high survival, polyfunctionality, proliferative capacity, metabolic plasticity, and antiviral potential. The development and...

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advan...

In spite of the efficacy of combinational antiretroviral treatment (cART), HIV-1 persists in the host and infection is associated with chronic inflammation, leading to an increased risk of comorbidities, such as cardiovascular diseases, neurocognitive disorders, and cancer. Myeloid cells, mainly monocytes and macrophages, have been shown to be invo...

Background Studies of antiretroviral drug (ARV) tissue distribution in preclinical models, such as mice, are key to understanding viral persistence. Objectives To determine the plasma and tissue pharmacokinetics and tissue distributions of tenofovir, emtricitabine and dolutegravir in mice. Methods ARVs were simultaneously administered to two diff...

New ways of characterizing CD8⁺ memory T cell responses in chronic infections are based on the measurement of chemokine receptor expression (CXCR3, CXCR5, and CX3CR1). We applied these novel phenotyping strategies to chronic HIV infection by comparing healthy donors (HDs), HIV‐infected patients receiving antiretroviral therapy (ART) and spontaneous...

Background: Myelin oligodendrocytes glycoprotein (MOG) antibody-associated disease (MOGAD) represent 25% of pediatric acquired demyelinating syndrome (ADS); 40% of them may relapse, mimicking multiple sclerosis (MS), a recurrent and neurodegenerative ADS, which is MOG-Abs negative. Aims: To identify MOG antigenic immunological response differences...

White adipose tissue (AT) contributes significantly to inflammation – especially in the context of obesity. Several of AT’s intrinsic features favor its key role in local and systemic inflammation: (i) large distribution throughout the body, (ii) major endocrine activity, and (iii) presence of metabolic and immune cells in close proximity. In obesi...

Monocyte HLA-DR is an increasingly recognized markers of sepsis-induced immunodepression, but its regulatory mechanisms remain poorly understood in sepsis. Several evidence for positive selection on the 5’ promoter region of HLA class II transactivator ( CIITA ) gene, the master regulator of MHC class II, have been gathered in the European populati...

Background: Interpretation of the increase in certain inflammatory markers in virally suppressed HIV-infected individuals must rely on an appropriate uninfected control group well characterized for non-HIV-related factors that contribute to chronic inflammation, e.g. smoking, alcohol consumption, or being overweight. We compared the inflammatory p...

Background Myeloid-derived suppressor cells (MDSC) are a functional myeloid cell subset that includes myeloid cells with immune suppressive properties. The presence of MDSC has been reported in the peripheral blood of patients with several malignant and non-malignant diseases. So far, direct comparison of MDSC across different diseases and Centers...

Background: Aging is characterized by adipose tissue senescence, inflammation, and fibrosis, with trunk fat accumulation. Aging HIV-infected patients have a higher risk of trunk fat accumulation than uninfected individuals-suggesting that viral infection has a role in adipose tissue aging. We previously demonstrated that HIV/SIV infection and the...

Background: Although some integrase strand transfer inhibitors (INSTIs) promote peripheral and central adipose tissue/weight gain in HIV-infected individuals, the underlying mechanism has not been identified. Here, we used human and simian models to assess the impact of INSTIs on adipose tissue phenotype and function. Methods: Adipocyte size and...

Although white AT can contribute to anti-infectious immune responses, it can also be targeted and perturbed by pathogens. The AT’s immune involvement is primarily due to strong pro-inflammatory responses (with both local and paracrine effects), and the large number of fat-resident macrophages. Adipocytes also exert direct antimicrobial responses. I...

Dendritic cells (DC), which are involved in orchestrating early immune responses against pathogens, are dysregulated in their function by HIV infection. This dysregulation likely contributes to tip the balance toward viral persistence. Different DC subpopulations, including classical (cDCs) and plasmacytoid (pDCs) dendritic cells, are subjected to...

This work sought to confirm the human‐like expression of exhaustion and senescence markers in a mouse model with a humanized immune system (HIS): the Balb/c Rag2KO IL2rgcKO SirpαNOD Flk2KO HLA‐A2HHD (BRGSF‐A2) mouse reconstituted with human CD34+ cord blood cells. With regard to senescence markers, the percentage of CD57+ T cells was higher in the...

Background: HIV infection has often been linked to faster immune aging. We sought to determine whether or not treatment-naïve spontaneous HIV-1 controllers (HICs) and ART-exposed patients differ with regard to the expression of cell senescence markers. Methods: Eighty-eight chronically infected HICs and ART-exposed patients (median time since in...

The proportion of Tregs in AT, as a function of the age of Foxp3-GFP reporter mice. The frequencies of Foxp3+ cells among CD4 T cells in SVF from SCAT (open symbols) and VAT (closed symbols) in male Foxp3-GFP mice aged 2–3, 12, and 18–22 months. Bars represent median values. Statistical significance was determined in a non-parametric Wilcoxon test...

Identification strategy for each subsets in the different species.

Although the metabolic properties of white adipose tissue have been extensively characterized, the tissue's immune properties are now attracting renewed interest. Early experiments in a mouse model suggested that white adipose tissue contains a high density of regulatory T cells (Tregs), and so it was assumed that all adipose tissue has an immunosu...

Objective: HIV-infected patients receiving antiretroviral treatment (ART) often present adipose tissue accumulation and/or redistribution. adipose tissue has been shown to be an HIV/SIV reservoir and viral proteins as Tat or Nef can be released by infected immune cells and exert a bystander effect on adipocytes or precursors. Our aim was to demons...

CD32a has been proposed as a specific marker of latently HIV-infected CD4⁺ T cells. However, CD32a was recently found to be expressed on CD4⁺ T cells of healthy donors, leading to controversy on the relevance of this marker in HIV persistence. Here, we used mass cytometry to characterize the landscape and variation in the abundance of CD32a⁺ CD4⁺ T...

Phenotypic landscape of CD4+ T-cell Spanning-tree Progression Analysis of Density-normalized Events (SPADE) clusters. A heatmap showing relative marker expression for SPADE clusters was generated. The mean of the median expression of each marker was determined and classified in a five-tiered color scale, from white (not expressed) to dark red (high...

Characterization of CD32a and CD32b antibody specificity by mass cytometry. Representative analysis of metal-conjugated CD32a-Dy161 (upper panels) and CD32b-Sm149 (lower panels) antibody staining of monocytes, B cells, and CD4+ T cells performed on PBMCs from one healthy donor (out of six) using FlowJo software.

Gating strategy used to identify CD4+ T cells. “Singlets” were identified using cell length vs. Ir191-DNA intercalator and calibration beads were excluded (cells no beads). Living leukocytes were identified by selecting Rhodium (Rh103)Di-negative cells and then CD45+ cells. Finally, CD4+ T cells were identified by gating on CD3+ CD19− and then CD4+...

Relative range of marker expression of Spanning-tree Progression Analysis of Density-normalized Events clusters. Graph showing the relative range of marker expression of clusters obtained after manual gating of CD4+ T cells. The range of expression for each marker (5th to 95th percentiles of expression throughout the dataset) are represented using...

Correlation analysis of total CD32a+ CD4+ T-cell cluster and cluster #5 cell abundances with HIV DNA levels. (A) Correlation analysis of total CD32a+ CD4+ T-cell cluster cell abundances with total HIV DNA levels. The HIV DNA load (log10 copies/106 PBMCs) for each sample are indicated on the X-axis, and the associated percentage of cells relative to...

Percentages of cells associated with clusters #5, #258, #136, #86, #261, #241, #162, #312, #243, #188, and #142 among CD4+ T cells in HIV-infected patients and healthy donors. (A–D) Graphs showing the cell abundance relative to that of CD4+ T cells for clusters previously shown to be differentially abundant between HIV-infected patients (primary HI...

Marker expression densities showing the phenotypic specificity of cluster #5 relative to whole CD4+ T-cell clusters. The expression densities of all clustering markers and CX3CR1 are shown for cluster #5 and whole CD4+ T-cell clusters. The marker expression densities for cluster #5 are shown in blue whereas the marker expression densities for all C...

Cell number in each CD32a+ CD4+ T-cell cluster. This representation shows the number of cells associated with each CD32a+ CD4+ T-cell cluster, regardless of sample cell origin. Cluster names are indicated on the X-axis and the corresponding number of cells on the Y-axis. The size of the dots is proportional to the number of cells in the cluster.

Percentages of CD32a+ CD4+ TN, TCM, and TEff/Mem subsets among CD4+ T cells from HIV-infected patients and healthy donors. This representation shows the percentage of naive (TN), central memory (TCM), and effector/memory (TEff/Mem) CD4+ T cells among CD32a+ CD4+ T cells for primary HIV-infected patients before (primary HIV, red circles) and after 1...

Overview of the mass cytometry panel. The metal, antigen, clone, isotype, and supplier are indicated for each antibody. Non-clustering markers are indicated by a star.

Classical dendritic cells (cDCs) play a pivotal role in the early events that tip the immune response toward persistence or viral control. In vitro studies indicate that HIV infection induces the dysregulation of cDCs through binding of the LILRB2 inhibitory receptor to its MHC-I ligands and the strength of this interaction was proposed to drive di...

[This corrects the article DOI: 10.1371/journal.pone.0190334.].

Interferons (IFNs) play a major role in controlling viral infections including HIV/SIV infections. Persistent up-regulation of interferon stimulated genes (ISGs) is associated with chronic immune activation and progression in SIV/HIV infections, but the respective contribution of different IFNs is unclear. We analyzed the expression of IFN genes an...

Comparison of the extent of IFNs and selected ISG expression in both phases of infection in RB, PLNs, and PBMCs. (PDF)

Functional enrichment of differentially expressed genes. (PDF)

The main IPA functions associated with D9-ISGs and M3-ISGs. (PDF)

Overlap between Interferome annotation and GAS/ISRE annotation of differentially induced ISGs. (PDF)

Functional enrichment analysis of PLNs, RBs, and PBMCs at D9 and M3. (XLSX)

primers and probes. (XLSX)

List of ISGs differentially expressed at either D9, M3, or both time points with their mean FC and associated functions. (XLSX)

Interferons play a major role in controlling viral infections including HIV/SIV infections. Persistent up-regulation of interferon-stimulated-genes (ISGs) is associated with chronic immune activation and progression in SIV/HIV infections, but the respective contribution of different IFNs is unclear. We analyzed the expression of annotated IFN-induc...

We and others have demonstrated that adipose tissue is a reservoir for HIV. Evaluation of the mechanisms responsible for viral persistence may lead to ways of reducing these reservoirs. Here, we evaluated the immune characteristics of adipose tissue in HIV-infected patients receiving antiretroviral therapy (ART) and in non-HIV-infected patients. We...

Two of the crucial aspects of human immunodeficiency virus (HIV) infection are (i) viral persistence in reservoirs (precluding viral eradication) and (ii) chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART)-controlled HIV-infected patients). The objective of the present study was to assess the potent...

The vast majority of Foxp3 regulatory T cells (Treg) exhibits constitutive expression of CD25 (IL-2Rα), which allows the constitution of the high affinity IL-2Rαβγ receptor, ensuring efficient IL-2 binding by Treg. Maintenance of CD25 expression at Treg surface depends on both cell intrinsic factors and environmental stimuli such as IL-2 itself. Wh...

CD4 T cell lymphopenia is an important T cell defect associated to ageing. Higher susceptibility to infections, cancer, or autoimmune pathologies described in aged individuals is thought to partly rely on T cell lymphopenia. We hypothesize that such diverse effects may reflect anatomical heterogeneity of age related T cell lymphopenia. Indeed, no d...

BACKGROUND:: Although HIV controllers (HICs) achieve long-term control of viremia in the absence of antiretroviral therapy (ART), they display marked immune activation. The levels of inflammatory biomarkers in HICs and the biomarkers' relationships with immunologic and virologic status have yet to be fully characterized. DESIGN:: A cohort study. ME...

The mineralocorticoid receptor (MR) exerts pro-adipogenic and anti-thermogenic effects in vitro, yet its in vivo metabolic impact remains elusive. Wild type (WT) and transgenic (Tg) mice overexpressing human MR were subjected to standard chow (SC) or high fat diet (HFD) for 16 wks. Tg mice had a lower body weight gain than WT animals, and exhibited...

The role of CD4+FOXP3+ regulatory T cells (Treg) in human immunodeficiency virus (HIV) infection has been an area of intensive investigation and remains a matter of ardent debate. Investigation and interpretation suffered from uncertainties concerning Treg quantification. Firstly, Treg quantification and function in HIV infection remain controversi...

Mechanisms governing peripheral CD4+ FOXP3+ regulatory T cells (Treg) survival and homeostasis are multiple suggesting tight and complex regulation of regulatory T cells homeostasis. Some specific factors, such as TGF-β, interleukin-2 (IL-2) and B7 costimulatory molecules have been identified as essentials for maintenance of the peripheral Treg com...

Regulatory T-cell (Treg) quantification in human immunodeficiency virus (HIV) infection remains ill defined because of the lack of reliable specific markers to identify human Tregs and the diversity of clinical stages of HIV infection. Using a recently described Treg identification strategy based on CD45RA and Foxp3 expression, we performed an exte...

Regulatory T cells (Treg) are commonly identified by CD25 (IL-2R alpha) surface expression and/or intracellular expression of the FOXP3 transcription factor. In addition, Treg are also characterized by low CD127 (IL-7R alpha) expression when compared to conventional T cells and their biology in the periphery is considered essentially independent of...

A model of chemical thymectomy by inducible Rag ablation was used to study peripheral T cell homeostasis. Induction of Rag ablation was efficient and complete, leading to cessation of thymic T cell production within 3–4 weeks. The decay of peripheral T cells became apparent with a delay of an additional 2–3 weeks and was entirely accounted for by l...

CD4 memory T cells surviving in the absence of MHC class II contact lose their characteristic memory function. To investigate the mechanisms underlying the impaired function of memory T cells in the absence of MHC class II molecules, we analyzed gene expression profiles of resting memory T cells isolated from MHC class II-competent or -deficient ho...

Homeostasis in the immune system is an important principle ensuring that the numbers of peripheral lymphocytes are kept more or less constant despite numerous disturbances in the immune system during the lifetime of an organism. Mechanisms relating to maintenance of homeostasis have mainly been investigated in experimental systems exhibiting extrem...

Lymphopenia has been associated with autoimmune pathology and it has been suggested that lymphopenia-induced proliferation of naive T cells may be responsible for the development of immune pathology. In this study we demonstrate that lymphopenia-induced proliferation is restricted to conditions of extreme lymphopenia, because neither naive nor memo...

CD4+ T cells are central regulators of both humoral and cellular immune responses. There are many subsets of CD4+ T cells, the most prominent being T-helper 1 (Th1), Th2, Th-17, and regulatory T cells, specialized in regulating different aspects of immunity. Without participation by these CD4+ T-cell subsets, B cells cannot undergo isotype switchin...