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Stéphanie Boisson-Dupuis

Publications and source records attributed to Stéphanie Boisson-Dupuis.

3 recordsLinked to original sources
PubMed2026

Human iPSC-derived alveolar macrophages reveal macrophage subtype functions of itaconate in M. tuberculosis defense.

Mycobacterium tuberculosis (Mtb) survives within multiple macrophage populations during infection, including alveolar macrophages (AMs) and recruited inflammatory macrophages. In mice, itaconate, produced in macrophages by ACOD1-mediated decarboxylation of aconitate, has direct antimicrobial activity, modulates inflammatory cytokines, and is required for resistance to Mtb infection. The role of itaconate in human macrophages is less clear, and it is unknown whether itaconate mediates distinct effects in macrophage subtypes. Here, we investigated the role of itaconate in macrophages derived from human induced pluripotent stem cells (iPSCs), induced by either GM-CSF to resemble AMs (AM-like cells, hereafter ipAM-Ls) or M-CSF to resemble monocyte-derived macrophages (MDM-like cells, hereafter ipMDM-Ls). Both human macrophage types produced substantially less itaconate than mouse macrophages, and ipAM-Ls produced 4-fold less itaconate than ipMDM-Ls. Surprisingly, ACOD1-deficient ipAM-Ls, but not ipMDM-Ls, were permissive for Mtb growth. Moreover, itaconate functioned to dampen the Mtb-induced inflammatory response in ipMDM-Ls, but not ipAM-Ls, affecting both the type I IFN and TNF pathways. These results indicate that itaconate is involved in human macrophage responses to tuberculosis, with distinct roles in different macrophage subsets. These results also show that genetically tractable iPSC-derived macrophages are a useful model to dissect cellular host-pathogen interactions in human macrophages.

Humans↗
PubMed2026

Human LFA-1 governs T cell immune surveillance of the skin.

The human integrin lymphocyte function-associated antigen 1 (LFA-1; αLβ2) is broadly expressed on leukocytes and involved in various intercellular adhesions. We report complete LFA-1 deficiency because of inherited αL (CD11a) deficiency in otherwise healthy adults of various ancestries with skin lesions due to commensal papillomaviruses. The patients had no history of invasive infections characteristic of children with inherited deficiency of β2 (CD18), which forms heterodimers with αL, αM (CD11b), αX (CD11c), or αD (CD11d). The development and function of leukocyte subsets are largely preserved in the absence of LFA-1. However, the transendothelial migration of skin-tropic cutaneous lymphocyte antigen (CLA)+ memory T cells is severely impaired, resulting in their selective sequestration in the blood. Conversely, alternative integrins mediate the extravasation of other leukocytes, including other T cell subsets, to other tissues. Human LFA-1 is required for steady-state T cell homing to the skin and control of papillomaviruses but is otherwise largely redundant. Integrin-mediated T cell compartmentalization is thus essential for organ-selective immune surveillance.

Humans↗
PubMed2024

Neutralizing IFN-γ autoantibodies are rare and pathogenic in HLA-DRB1*15:02 or 16:02 individuals.

BACKGROUNDWeakly virulent environmental mycobacteria (EM) can cause severe disease in HLA-DRB1*15:02 or 16:02 adults harboring neutralizing anti-IFN-γ autoantibodies (nAIGAs). The overall prevalence of nAIGAs in the general population is unknown, as are the penetrance of nAIGAs in HLA-DRB1*15:02 or 16:02 individuals and the proportion of patients with unexplained, adult-onset EM infections carrying nAIGAs.METHODSThis study analyzed the detection and neutralization of anti-IFN-γ autoantibodies (auto-Abs) from 8,430 healthy individuals of the general population, 257 HLA-DRB1*15:02 or 16:02 carriers, 1,063 patients with autoimmune disease, and 497 patients with unexplained severe disease due to EM.RESULTSWe found that anti-IFN-γ auto-Abs detected in 4,148 of 8,430 healthy individuals (49.2%) from the general population of an unknown HLA-DRB1 genotype were not neutralizing. Moreover, we did not find nAIGAs in 257 individuals carrying HLA-DRB1* 15:02 or 16:02. Additionally, nAIGAs were absent in 1,063 patients with an autoimmune disease. Finally, 7 of 497 patients (1.4%) with unexplained severe disease due to EM harbored nAIGAs.CONCLUSIONThese findings suggest that nAIGAs are isolated and that their penetrance in HLA-DRB1*15:02 or 16:02 individuals is low, implying that they may be triggered by rare germline or somatic variants. In contrast, the risk of mycobacterial disease in patients with nAIGAs is high, confirming that these nAIGAs are the cause of EM disease.FUNDINGThe Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI095983 and U19AIN1625568), the National Center for Advancing Translational Sciences (NCATS), the NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), the French National Research Agency (ANR) under the "Investments for the Future" program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), ANR-GENMSMD (ANR-16-CE17-0005-01), ANR-MAFMACRO (ANR-22-CE92-0008), ANRSECTZ170784, the French Foundation for Medical Research (FRM) (EQU201903007798), the ANRS-COV05, ANR GENVIR (ANR-20-CE93-003), and ANR AI2D (ANR-22-CE15-0046) projects, the ANR-RHU program (ANR-21-RHUS-08-COVIFERON), the European Union's Horizon 2020 research and innovation program under grant agreement no. 824110 (EASI-genomics), the Square Foundation, Grandir - Fonds de solidarité pour l'enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, the Battersea & Bowery Advisory Group, William E. Ford, General Atlantic's Chairman and Chief Executive Officer, Gabriel Caillaux, General Atlantic's Co-President, Managing Director, and Head of business in EMEA, and the General Atlantic Foundation, Institut National de la Santé et de la Recherche Médicale (INSERM) and of Paris Cité University. JR was supported by the INSERM PhD program for doctors of pharmacy (poste d'accueil INSERM). JR and TLV were supported by the Bettencourt-Schueller Foundation and the MD-PhD program of the Imagine Institute. MO was supported by the David Rockefeller Graduate Program, the Funai Foundation for Information Technology (FFIT), the Honjo International Scholarship Foundation (HISF), and the New York Hideyo Noguchi Memorial Society (HNMS).

Adult↗