Anne Hosmalin

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Anne Hosmalin, MD PhD is a Research Director at the National Center for Scientific Research (CNRS). She is Director of a research team on " Dendritic Cells, immunostimulation of viral and tumoral micro environments » at Institut Cochin in Paris, and Director of the Immunology and Immunopathology IHM, Université Paris-Cité. She is a former President of the French Society for Immunology (SFI). She works on the role of dendritic and myeloid cells in the pathogenesis of HIV and on antigen presentation by dendritic cells.

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Review for "Guidelines for DC preparation and flow cytometric analysis of human lymphohematopoietic tissues

Reduced blood CD123+ (lymphoid) and CD11c+ (myeloid) dendritic cell numbers in primary HIV-1 infection

by Pierre Lebon and Anne Hosmalin

Blood, 2001

Successful immunologic control of HIV infection is achieved only in rare individuals. Dendritic c... more Successful immunologic control of HIV infection is achieved only in rare individuals. Dendritic cells (DCs) are required for specific antigen presentation to naive T lymphocytes and for antiviral, type I interferon secretion. Two major blood DC populations are found: CD11c+ (myeloid) DCs, which secrete IL-12, and CD123+ (IL-3–receptor+) DCs (lymphoid), which secrete type I interferons in response to viral stimuli. The authors have previously found a decreased proportion of blood CD11c+ DCs in chronic HIV+ patients. In this study, 26 to 57 days after infection and before treatment, CD123+ and CD11c+ DC numbers were dramatically reduced in 13 HIV+ patients compared with 13 controls (P = .0002 and P = .001, respectively). After 6 to 12 months of highly active antiretroviral therapy, DC subpopulation average numbers remained low, but CD123+ DC numbers increased again in 5 of 13 patients. A strong correlation was found between this increase and CD4 T-cell count increase (P = .0009) and p...

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Current status of the LHRH immunization approach

PubMed, 1987

Human Immunodeficiency Virus Reverse Transcriptase T Helper Epitopes Identified in Mice and Humans: Correlation with a Cytotoxic T Cell Epitope

The Journal of Infectious Diseases, Dec 1, 1991

ABSTRACT

Circulating myeloid and plasmacytoid dendritic cells are strongly diminished in septic shock

Critical Care, 2008

Background The morbidity and mortality from severe sepsis depends largely on how quickly and comp... more Background The morbidity and mortality from severe sepsis depends largely on how quickly and comprehensively evidencebased therapies are administered. As such, a huge opportunity exists. However, optimal care requires not only factual knowledge, but also numerous practical strategies including the ability to recognize a disease, to identify impending crises, to communicate effectively, to run a team, to work under stress and to simultaneously coordinate multiple tasks. Medical simulation offers a way to practice these essential crisis management skills, and without any risk to patients. Methods Following a didactic lecture on the key components of the Surviving Sepsis Campaign Guidelines, we trained 20 emergency medicine residents on a portable Laerdal Patient Simulator. Pre-programmed sepsis scenarios were developed following a needs assessment and modified Delphi technique. To maximize realism, this was performed in the acute care area of the Emergency Department and included a pre-briefed respiratory therapist and nurse. We videotaped resident performance and provided nonpunitive feedback, focusing on the comprehensiveness of therapy (for example, whether broad-spectrum antibiotics were given) and crisis resource management strategies (for example, whether help was asked for and tasks were appropriately allocated). Results Evaluation using a five-point Likert scale demonstrated that participants found this very useful (4.5/5), that lessons were complementary and supplementary to those learned from lectures (4.5/5) and that medical simulation was realistic (4/5). In addition, despite prior sepsis lectures, comparison of pre-tests and posttests showed that more emergency medicine residents would: administer broad-spectrum antibiotics as soon as possible following hypotension (14/20 pre-test, compared with 16/20 posttest), administer low-dose corticosteroids for those with refractory shock (10/20 pre-test, compared with 13/20 post-test), and would favour norepinephrine as a vasopressor (8/20 pre-test, compared with 12/20 post-test). Participants specifically valued the chance to observe and practice crisis resource management skills, which they felt had not been previously addressed (19/20). Conclusion Medical simulation appears to be an effective way to change both knowledge and behaviours in the treatment of severe sepsis. Many education and licensing boards also expect trainees to become not only content experts, but also effective communicators, collaborators, resource managers and advocates. These laudable goals are difficult to capture with traditional lectures but are comparably easy using medical simulation. We hope others will consider medical simulation as a complementary teaching and quality-assurance strategy in the fight against sepsis. P2 Protective potential of 2-chloroadenosine in Klebsiella pneumoniae B5055 induced sepsis in BALB/c mice

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Cytosolic PCNA interacts with S100A8 and controls an inflammatory subset of neutrophils in COVID-19

Neutrophils are key players in the hyperinflammatory response upon SARS-CoV-2 infection. We have ... more Neutrophils are key players in the hyperinflammatory response upon SARS-CoV-2 infection. We have previously described that cytosolic proliferating cell nuclear antigen (PCNA) controls neutrophil survival and NADPH oxidase-dependent ROS production. We here show that both PCNA and S100A8 expression and interaction were elevated in neutrophils from patients with COVID-19 compared to healthy donors and this was correlated with disease severity. Increased PCNA expression was accompanied by a decreased apoptosis and increased NADPH-oxidase activity in neutrophils from COVID-19 patients compared to healthy donors. These effects, as well as the interaction between PCNA and S100A8, were potently counteracted by T2 amino alcohol (T2AA), a PCNA inhibitor, demonstrating that the PCNA scaffold orchestrated neutrophil activation. Notably, the interaction between PCNA-S100A8 was more intense in the CD16high-CD62Llowactivated neutrophil subset. We propose that PCNA-S100A8 complex acts as potential ...

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mediators in pathogenic SIVmac and non-pathogenic SIVagm infections

Activation of dopamine 1 receptors in human neuronal-like cells transdifferentiated from blood circulating monocytes replicates findings from <i>in vivo</i> studies

Monitoring antigen cross-presentation by human dendritic cells purified from peripheral blood

Methods in Enzymology, 2020

Tumor immunosurveillance, regression and therapy require most often the action of CD8+ T cells. T... more Tumor immunosurveillance, regression and therapy require most often the action of CD8+ T cells. These cells are primed by dendritic cells (DC), which are the only antigen presenting cells able to stimulate naive T cells. Tumor antigen presentation requires cross-presentation of antigens from the tumor cells by DC. Dendritic cells capture antigens from tumor cells into endosomal compartments and process them. Then they expose at their cell surface their own MHC class I molecules complexed with tumor cell epitopes, which are recognized by the T cell receptors of specific CD8+ T cells. This allows the activation of anti-tumoral functions of these specific CD8+ T cells, mediated by cytokines and by cytotoxic mechanisms. Here, we describe in detail the delicate methods required to (1) prepare antigen donor cells, (2) prepare CD8+ T cells specific for these antigens, (3) purify human DC from peripheral blood, (4) preincubate purified DC and antigen donor cells for antigen capture, (5) incubate these DC with antigen-specific CD8+ T cells for cross-presentation and (6) assess cross-presentation to specific CD8+ T cells. These methods allowed our laboratory to characterize in detail cross-presentation from cells containing viral antigens and can be applied to study cross-presentation from tumor antigens.

HIV-1 reservoirs in urethral macrophages of patients under suppressive antiretroviral therapy

Nature Microbiology, 2019

Human immunodeficiency virus type 1 (HIV-1) eradication is prevented by the establishment on infe... more Human immunodeficiency virus type 1 (HIV-1) eradication is prevented by the establishment on infection of cellular HIV-1 reservoirs that are not fully characterized, especially in genital mucosal tissues (the main HIV-1 entry portal on sexual transmission). Here, we show, using penile tissues from HIV-1-infected individuals under suppressive combination antiretroviral therapy, that urethral macrophages contain integrated HIV-1 DNA, RNA, proteins and intact virions in virus-containing compartment-like structures, whereas viral components remain undetectable in urethral T cells. Moreover, urethral cells specifically release replication-competent infectious HIV-1 following reactivation with the macrophage activator lipopolysaccharide, while the T-cell activator phytohaemagglutinin is ineffective. HIV-1 urethral reservoirs localize preferentially in a subset of polarized macrophages that highly expresses the interleukin-1 receptor, CD206 and interleukin-4 receptor, but not CD163. To our knowledge, these results are the first evidence that human urethral tissue macrophages constitute a principal HIV-1 reservoir. Such findings are determinant for therapeutic strategies aimed at HIV-1 eradication.

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Circulating dendritic cells and interferon-α production in patients with tuberculosis: correlation with clinical outcome and treatment response

Clinical and Experimental Immunology, 2006

Summary Dendritic cells (DC) have been characterized recently as having an important role in the ... more Summary Dendritic cells (DC) have been characterized recently as having an important role in the initiation and control of immunological response to Mycobacterium tuberculosis infection. Blood DC have been subdivided into myeloid (mDC) and plasmacytoid (pDC) subsets, on the basis of differences in phenotype markers and function. Little is known about the enumeration and functional evaluation of circulating DC in patients with tuberculosis and their correlation with clinical outcome during the course of anti-tuberculous treatment. We assessed circulating mDC and pDC counts measured by a newly developed single-platform flow cytometric assay based on TruCOUNT, as well as the production of interferon (IFN)-α after in vitro stimulation by herpes simplex virus (HSV-1) in 24 patients with active tuberculosis (TB) and 37 healthy donors. Absolute numbers of both DC subsets were decreased significantly in patients with active TB compared to controls. Similarly, the production of IFN-α was hig...

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A Comparison of Cell Activation, Exhaustion, and Expression of HIV Coreceptors and Restriction Factors in HIV-1- and HIV-2-Infected Nonprogressors

AIDS Research and Human Retroviruses

BACKGROUND Human Immunodeficiency Viruses induce rare attenuated diseases due either to HIV-1 in ... more BACKGROUND Human Immunodeficiency Viruses induce rare attenuated diseases due either to HIV-1 in the exceptional Long Term Non-Progressors (LTNPs) or to HIV-2 in West-Africa. To better understand characteristics of these two disease types we performed a multiplex comparative analysis of cell activation, exhaustion and expression of co-receptors and restriction factors in CD4 T cells susceptible to harbor those viruses. METHODS we analyzed by flow cytometry the expression of HLA-DR, PD1, CCR5, CXCR6, SAMHD1, Blimp-1, TRIM5α on CD4 T cell subsets from 10 HIV-1+ LTNPs and 14 HIV-2+ Non Progressors (NPs) of the ANRS CO-15 and CO-5 cohorts, respectively, and 12 HIV- healthy donors (HD). The V3 loop of the HIV-1 envelope from 6 HIV-1+ LTNPs was sequenced to determine CXCR6 binding capacity. RESULTS Proportions of HLA-DR+ and PD1+ cells were higher in memory CD4 T subsets from HIV-1 LTNPs compared to HIV-2 and HD. Similar findings were observed for CCR5+ cells though limited to TCM and follicular helper T cells subsets while all major subsets from HIV-1 LTNPs contained less CXCR6+ cells compared to HIV-2. All six V3 loop sequences from HIV-1 LTNPs contained a proline at position 326. Proportions of SAMHD1+ cells were higher in all resting CD4 T subsets from HIV-1 LTNPs compared to the other groups while Blimp-1+ and Trim5α+ cells did not differ. CONCLUSION The CD4 T cell subsets from HIV-1 LTNPs differ from those of HIV-2 NPs by higher levels of activation, exhaustion and SAMHD1 expression that can reflect the distinct patterns of host-virus relationships.

HIV-1 and HIV-2 induce Interferon-lambda production by plasmacytoid Dendritic Cells

The Journal of Immunology

Type III Interferons (IFN-λ) were barely studied during HIV infection, despite their antiviral pr... more Type III Interferons (IFN-λ) were barely studied during HIV infection, despite their antiviral properties similar to those of type I IFN and their important role during HCV infection, where IFN-λ3 gene polymorphisms correlate with viral clearance. We tested IFN-λ responses to HIV-1, and also to HIV-2, which is less pathogenic. We first stimulated PBMC (EFS-Inserm convention) enriched for dendritic cells (DC), the main IFN producers. Purified HIV-1 virions or H9 T cells chronically infected with HIV-1 induced transcription of IFN-λ1 and 2/3 mRNA (RT-qPCR), as well as the secretion of IFN-λ (ELISA). Similar results were obtained with HIV-2-infected cells or virions. Intracellular labeling for IFN-λ1 was detected by flow cytometry in BDCA-4+ plasmacytoid DC (pDC), but not in BDCA-1+ or -3+ conventional DC (cDC). This was confirmed in > 95% purified cell populations. Recognition of HIV-1 or HIV-2 by pDC induced their maturation (surface CD83 and CCR7 overexpression), and bystander ma...

A tribute to Nilabh Shastri and a special issue on antigen processing and presentation in Paris (APP10, Paris 2019)

Molecular Immunology, 2022

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Cellules dendritiques et infection par le VIH

Virologie, 1999

Les cellules dendritiques sont des leucocytes qui presentent les antigenes aux lymphocytes T. Ell... more Les cellules dendritiques sont des leucocytes qui presentent les antigenes aux lymphocytes T. Elles sont les seules cellules presentatrices capables d’activer les lymphocytes T naifs lors d’une immunisation primaire, et elles sont optimales pour activer les T memoire. Les cellules dendritiques sont infectees in vivo par le VIH, mais avec une faible frequence, ainsi que leurs homologues les cellules de Langerhans, presentes dans la peau et les muqueuses pluristratifiees. Elles representent dans ces muqueuses une porte d’entree tres probable du VIH. Elles transportent ensuite le virus vers les regions T des ganglions drainants, ou elles transmettent l’infection aux lymphocytes T. Les corecepteurs qu’elles expriment en plus de CD4 et leur capacite de repliquer et de transmettre les virus dependent de leur stade de maturation. Immatures, elles sont principalement permissives a la penetration et la replication des souches R5 (monocytotropes), qu’elles transmettent aux T qui en retour ind...

Limited HIV-2 reservoirs in central-memory CD4 T-cells associated to CXCR6 co-receptor expression in attenuated HIV-2 infection

PLOS Pathogens, 2019

The low pathogenicity and replicative potential of HIV-2 are still poorly understood. We investig... more The low pathogenicity and replicative potential of HIV-2 are still poorly understood. We investigated whether HIV-2 reservoirs might follow the peculiar distribution reported in models of attenuated HIV-1/SIV infections, i.e. limited infection of central-memory CD4 T lymphocytes (TCM). Antiretroviral-naive HIV-2 infected individuals from the ANRS-CO5 (12 non-progressors, 2 progressors) were prospectively included. Peripheral blood mononuclear cells (PBMCs) were sorted into monocytes and resting CD4 T-cell subsets (naive [TN], central-[TCM], transitional-[TTM] and effector-memory [TEM]). Reactivation of HIV-2 was tested in 30-day cultures of CD8-depleted PBMCs. HIV-2 DNA was quantified by real-time PCR. Cell surface markers, co-receptors and restriction factors were analyzed by flowcytometry and multiplex transcriptomic study. HIV-2 DNA was undetectable in monocytes from all individuals and was quantifiable in TTM from 4 individuals (median: 2.25 log 10 copies/10 6 cells [IQR: 1.99-2.94]) but in TCM from only 1 individual (1.75 log 10 copies/10 6 cells). HIV-2 DNA levels in PBMCs (median: 1.94 log 10 copies/10 6 PBMC [IQR = 1.53-2.13]) positively correlated with those in TTM (r = 0.66, p = 0.01) but not TCM. HIV-2 reactivation was observed in the cells from only 3 individuals. The CCR5 co-receptor was distributed similarly in cell populations from individuals and donors. TCM had a lower expression of CXCR6 transcripts (p = 0.002) than TTM confirmed

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blood-2012-Dutertre-03-418681 Supplemental data

M-DC8+ Monocyte Depleting Agent for the Prevention or the Treatment of a Condition Associated with a Chronic Hyperactivation of the Immune System

Method for in Vitro Differentiation of Blood Circulating Cells Into Neuronal-Like Cells and Applications Thereof

Distinct expression profiles of TGF-beta1 signaling mediators in pathogenic SIVmac and non-pathogenic SIVagm infections

Retrovirology, Jan 26, 2006

The generalized T-cell activation characterizing HIV-1 and SIVmac infections in humans and macaqu... more The generalized T-cell activation characterizing HIV-1 and SIVmac infections in humans and macaques (MACs) is not found in the non-pathogenic SIVagm infection in African green monkeys (AGMs). We have previously shown that TGF-beta1, Foxp3 and IL-10 are induced very early after SIVagm infection. In SIVmac-infected MACs, plasma TGF-beta1 induction persists during primary infection 1. We raised the hypothesis that MACs are unable to respond to TGF-beta1 and thus cannot resorb virus-driven inflammation. We therefore compared the very early expression dynamics of pro- and anti-inflammatory markers as well as of factors involved in the TGF-beta1 signaling pathway in SIV-infected AGMs and MACs. Levels of transcripts encoding for pro- and anti-inflammatory markers (tnf-alpha, ifn-gamma, il-10, t-bet, gata-3) as well as for TGF-beta1 signaling mediators (smad3, smad4, smad7) were followed by real time PCR in a prospective study enrolling 6 AGMs and 6 MACs. During primary SIVmac infection, up...

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Anne Hosmalin

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