Publications by authors named "Delphine M Depierreux"

Introduction: Involved in immunity and reproduction, natural killer (NK) cells offer opportunities to develop new immunotherapies to treat infections and cancer or to alleviate pregnancy complications. Most current strategies use cytokines or antibodies to enhance NK-cell function, but none use ion channel modulators, which are widely used in clinical practice to treat hypertension, diabetes, epilepsy, and other conditions. Little is known about ion channels in NK cells.

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The recurring spillover of pathogenic coronaviruses and demonstrated capacity of sarbecoviruses, such SARS-CoV-2, to rapidly evolve in humans underscores the need to better understand immune responses to this virus family. For this purpose, we characterized the functional breadth and potency of antibodies targeting the receptor binding domain (RBD) of the spike glycoprotein that exhibited cross-reactivity against SARS-CoV-2 variants, SARS-CoV-1 and sarbecoviruses from diverse clades and animal origins with spillover potential. One neutralizing antibody, C68.

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Involved in immunity and reproduction, natural killer (NK) cells offer opportunities to develop new immunotherapies to treat infections and cancer or to alleviate pregnancy complications. Most current strategies use cytokines or antibodies to enhance NK-cell function, but none use ion channel modulators, which are widely used in clinical practice to treat hypertension, diabetes, epilepsy, and other conditions. Little is known about ion channels in NK cells.

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Article Synopsis
  • The SARS-CoV-2 virus has evolved to evade immune responses created by vaccines and previous infections, particularly through mutations in the spike protein's receptor binding domain.
  • Researchers identified a group of S2 mAbs from convalescent individuals that target various regions in the spike protein, including one powerful mAb, C20.119, which effectively neutralizes multiple SARS-CoV-2 variants.
  • Some mAbs displayed antibody-dependent cellular cytotoxicity (ADCC) and targeted regions of the spike protein that could lead to effective treatments, suggesting potential for developing new therapies for future pandemics.
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Article Synopsis
  • The study highlights the need to understand immune responses to pathogenic coronaviruses, particularly in the context of rapid evolution, using antibodies targeting the receptor binding domain (RBD) of the spike glycoprotein.
  • An antibody named C68.61 was identified for its exceptional ability to neutralize SARS-CoV-2 variants as well as other sarbecoviruses without leading to escape variants, indicating a conserved target epitope.
  • The research also discovered 11 additional cross-reactive antibodies that can potentially serve as therapeutic options for pandemic preparedness by recognizing conserved regions across multiple sarbecoviruses.
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Natural killer (NK) cells have an established role in controlling poxvirus infection and there is a growing interest to exploit their capabilities in the context of poxvirus-based oncolytic therapy and vaccination. How NK cells respond to poxvirus-infected cells to become activated is not well established. To address this knowledge gap, we studied the NK cell response to vaccinia virus (VACV) , using a systemic infection murine model.

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The interaction between immune cells and virus-infected targets involves multiple plasma membrane (PM) proteins. A systematic study of PM protein modulation by vaccinia virus (VACV), the paradigm of host regulation, has the potential to reveal not only novel viral immune evasion mechanisms, but also novel factors critical in host immunity. Here, >1000 PM proteins were quantified throughout VACV infection, revealing selective downregulation of known T and NK cell ligands including HLA-C, downregulation of cytokine receptors including IFNAR2, IL-6ST and IL-10RB, and rapid inhibition of expression of certain protocadherins and ephrins, candidate activating immune ligands.

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Reproductive immunology has moved on from the classical Medawar question of 60 years ago "". Looking beyond fetal-maternal tolerance, modern reproductive immunology focuses on how the maternal immune system supports fetal growth. Maternal uterine natural killer (uNK) cells, in partnership with fetal trophoblast cells, regulate physiological vascular changes in the uterus of pregnant women and mice.

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Described here is a simple method to isolate and phenotype mouse group 1 uterine innate lymphoid cells (g1 uILCs) from individual pregnant uterus by flow cytometry. The protocol describes how to set up time mating to obtain multiple synchronous dams, the mechanical and enzymatic digestion of the pregnant uterus, the staining of single-cell suspensions, and a FACS strategy to phenotype and discriminate g1 uILCs. Although this method inevitably loses the spatial information of cellular distribution within the tissue, the protocol has been successfully applied to determine uILC heterogeneity, their response to maternal and foetal factors affecting pregnancy, their gene expression profile, and their functions.

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