A5023377101- Tuberculosis Research and Epidemiology
- Adenosine and Purinergic Signaling
- Immune Response and Inflammation
- Pneumocystis jirovecii pneumonia detection and treatment
- Neuropeptides and Animal Physiology
- Immune cells in cancer
- Immune Cell Function and Interaction
- interferon and immune responses
- Inflammasome and immune disorders
- Pharmacological Receptor Mechanisms and Effects
- Heme Oxygenase-1 and Carbon Monoxide
- Cancer, Stress, Anesthesia, and Immune Response
- Inflammation biomarkers and pathways
- Ferroptosis and cancer prognosis
- RNA modifications and cancer
- Science and Education Research
- Cancer Immunotherapy and Biomarkers
- T-cell and Retrovirus Studies
- Cytokine Signaling Pathways and Interactions
- Synthesis and biological activity
- Synthesis and Characterization of Heterocyclic Compounds
- Cancer-related molecular mechanisms research
- Neonatal Health and Biochemistry
- Immunodeficiency and Autoimmune Disorders
- Pediatric health and respiratory diseases
Institut de Pharmacologie et de Biologie Structurale
2025
Institut Cochin
2023-2024
Université Paris Cité
2023-2024
Inserm
2023-2024
Centre National de la Recherche Scientifique
2023-2024
National Institute of Allergy and Infectious Diseases
2020-2023
National Institutes of Health
2020-2022
Universidade de São Paulo
2014-2022
Universidade Federal da Paraíba
2015
Cellular necrosis during Mycobacterium tuberculosis (Mtb) infection promotes both immunopathology and bacterial dissemination. Glutathione peroxidase-4 (Gpx4) is an enzyme that plays a critical role in preventing iron-dependent lipid peroxidation–mediated cell death (ferroptosis), process previously implicated the necrotic pathology seen Mtb-infected mice. Here, we document altered GPX4 expression, glutathione levels, peroxidation patients with active assess of this pathway mice genetically...
The purinergic P2X7 receptor (P2X7R) is a sensor of extracellular ATP, damage-associated molecule that released from necrotic cells and induces pro-inflammatory cytokine production cell death. To investigate whether the innate immune response to damage signals could contribute development pulmonary lesions in severe forms tuberculosis, disease progression was examined C57BL/6 P2X7R−/− mice were intratracheally infected with highly virulent mycobacterial strains (Mycobacterium tuberculosis...
Irg1 is an enzyme that generates itaconate, a metabolite plays key role in the regulation of inflammatory responses. Previous studies have implicated as important mediator preventing excessive inflammation and tissue damage Mycobacterium tuberculosis (Mtb) infection. Here, we investigated pattern recognition receptors signaling pathways by which Mtb triggers gene expression comparing responses control genetically deficient BMDMs. Using this approach, demonstrated partial roles for TLR-2 (but...
Abstract Oxidative stress triggers ferroptosis, a form of cellular necrosis characterized by iron-dependent lipid peroxidation, and has been implicated in Mycobacterium tuberculosis (Mtb) pathogenesis. We investigated whether Bach1, transcription factor that represses multiple antioxidant genes, regulates host resistance to Mtb. found BACH1 expression is associated clinically with active pulmonary tuberculosis. Bach1 deletion Mtb-infected mice increased glutathione levels Gpx4 inhibit...
Mycobacterium tuberculosis (Mtb) infection induces pulmonary expression of the heme-degrading enzyme heme oxygenase-1 (HO-1). We have previously shown that pharmacological inhibition HO-1 activity in experimental results decreased bacterial loads and unexpectedly this outcome depends on presence T lymphocytes. Here, we extend these findings by demonstrating IFNγ production lymphocytes NOS2 underlie T-cell requirement potentiates IFNγ-induced NOS2-dependent control Mtb macrophages vitro....
Upon its mucosal transmission, HIV type 1 (HIV-1) rapidly targets genital antigen-presenting Langerhans cells (LCs), which subsequently transfer infectious virus to CD4+ T cells. We previously described an inhibitory neuroimmune cross talk, whereby calcitonin gene-related peptide (CGRP), a neuropeptide secreted by peripheral pain-sensing nociceptor neurons innervating all epithelia and associating with LCs, strongly inhibits HIV-1 transfer. As nociceptors secret CGRP following the activation...
Abstract In 2020–2021, a “mysterious illness” struck Senegalese fishermen, causing severe acute dermatitis in over one thousand individuals following exposure through drift-net fishing activity. Here, by performing deep analysis of the environmental samples we reveal presence marine dinoflagellate Vulcanodinium rugosum and its associated cyclic imine toxins. Specifically, show that toxin PortimineA, strongly enriched samples, impedes ribosome function human keratinocytes, which subsequently...
The risk of developing severe forms tuberculosis has increased by the acquired immunodeficiency syndrome (AIDS) epidemic, lack effective drugs to eliminate latent infection and emergence drug-resistant mycobacterial strains. Excessive inflammatory response tissue damage associated with contribute poor outcome disease. Our previous studies using mice deficient in ATP-gated ionotropic P2X7 receptor suggested this molecule as a promising target for host-directed therapy pulmonary tuberculosis....
Tuberculosis (TB) remains a serious public health problem despite the great scientific advances in recent decades. We have previously shown that aggressive forms of TB caused by hypervirulent strains Mycobacterium tuberculosis and bovis are attenuated mice lacking P2X7 receptor, an ion channel activated extracellular ATP. Therefore, receptor is potential target for therapeutic intervention. In vitro, mycobacteria cause macrophage death P2X7-dependent mechanism facilitates bacillus...
Abstract Background The role of myeloid-derived suppressor cells (MDSCs) in patients with severe tuberculosis who suffer from uncontrolled pulmonary inflammation caused by hypervirulent mycobacterial infection remains unclear. Methods This issue was addressed using C57BL/6 mice infected highly virulent Mycobacterium bovis strain MP287/03. Results CD11b+GR1int population increased the bone marrow, blood and lungs during advanced disease. Pulmonary (Ly6GintLy6Cint) showed granularity similar...
Tuberculous pneumonia, necrotic granulomatous lesions, and bacterial dissemination characterize severe forms of mycobacterial infection.To evaluate the pulmonary CD4+ T-cell response during tuberculosis, C57BL/6 mice were infected with approximately 100 bacilli 3 hypervirulent isolates (Mycobacterium tuberculosis strain Beijing 1471 Mycobacterium bovis strains B2 MP287/03) or H37Rv M as reference for virulence. Because high expression both CD39 CD73 ectonucleotidases was detected on...
The Morita-Baylis-Hillman reaction is an organocatalyzed chemical transformation that allows access to small poly-functionalized molecules and has considerable synthetic potential promising biological profiles. adducts (MBHA) are a new class of bioactive compounds highlight its potentialities the discovery cheaper efficient drugs, e.g. as anti-Leishmania chagasi Leishmania amazonensis, anti- Trypanosoma cruzi, anti-Plasmodium falciparum Plasmodium berghei, lethal against Biomphalaria...
Abstract X‐linked ectodermal dysplasia with immunodeficiency (XL‐EDA‐ID) is caused by mutations in the nuclear factor‐kappa B essential modulator ( NEMO ) gene. Here, we report clinical and genetic features of a XL‐EDA‐ID patient who developed bacillus Calmette–Guérin infection. Patient lymphocytes failed to degrade IκB‐α, sequencing identified novel mutation c.1238A>C/p.H413P. Furthermore, monocyte‐derived macrophages ingested Mycobacterium tuberculosis normally, but control...
The interplay between M.tuberculosis (Mtb) and humans is multifactorial. susceptibility/resistance profile the establishment of clinical tuberculosis (TB) still remains elusive. gain-of-function variant rs10754558 in NLRP3 gene (found 30% world population) confers protection against development TB, indicating a prominent role inflammasome Mtb. Through genotype-guided assays various Mtb strains (BCG, H37Rv, Beijing-1471, MP287/03), we demonstrated that activate according to NLRP3/IL-1ß or...
Upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), patients critical disease 2019 (COVID-19) present life-threatening distress, pulmonary damage, and cytokine storm. One unexplored component in COVID-19 is the neuropeptide calcitonin gene-related peptide (CGRP), which highly abundant airways could converge multiple aspects of COVID-19-related pathophysiology. Whether CGRP affects SARS-CoV-2 directly remains elusive. We show that patients, increased both plasma...
Abstract Ferroptosis is a type of regulated necrotic cell death induced by the acumulation free iron and lipid peroxides. We have previously described role for ferroptosis in Mtb-induced macrophage necrosis based on its biochemical requirements blockade both vitro vivo peroxidation inhibitor (fer-1). To help validate these findings further delineate mechanism involved we analyzed cellular host resistance mice deficient or overexpressing glutathione peroxidase (Gpx4), an essential regulator...
Abstract Upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), patients critical disease 2019 (COVID-19) present life-threatening distress, pulmonary damage and cytokine storm. One unexplored hub in COVID-19 is the neuropeptide calcitonin gene-related peptide (CGRP), which highly abundant airways could converge multiple aspects of COVID-19-related pathophysiology. Whether CGRP affects SARS-CoV-2 directly remains elusive. We show that patients, increased both...
<h3>Background</h3> CD40 ligand (CD40L) deficiency predisposes to opportunistic infections including those caused by fungi and intracellular bacteria. Studies of CD40L-deficient patients reveal the critical role CD40L-CD40 interaction for function T, B, dendritic cells. However, consequences CD40L on macrophage remain poorly understood. <h3>Objectives</h3> To analzye in macrophages immune response. <h3>Methods</h3> MDMs were challenged with <i>Paracoccidioides brasiliensis</i> (Pb18, a...
Abstract CD4+ T cells are crucial to control pulmonary tuberculosis, but also favor uncontrolled inflammation in severe disease. Effective cell response tuberculosis is related tissue location: Lung-resident display higher effector function comparison circulating cells. Among the factors favoring residency non-lymphoid tissues, extracellular ATP sensing via P2RX7 for generation of virus-specific resident memory CD8+ Yet, its role has not been defined. Moreover, mycobacterial infection...