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Neuroendocrine control of natural killer cell function through the checkpoint molecule PD-1

Cellular & Molecular Immunology volume 16, pages 109–111 (2019)Cite this article

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Host defense strategies encompass resistance to reduce pathogen burden, and disease tolerance to preserve host fitness.1 Immune-driven resistance mechanisms have inevitably a negative impact on host fitness and can lead to immunopathology. Disease tolerance limit immunopathology and therefore disease severity by preventing tissue damage or ameliorating tissue function without interfering with pathogen load. Several pathways cooperate to protect the host. These pathways include metabolic and oxidative stress responses,2 and the interaction between neuroendocrine system and the immune system3 to favor resolution of inflammation and to prevent tissue damage.

It has long been recognized a complex functional linkage between the immune and the nervous systems. In infectious insults, proinflammatory cytokines activate the hypothalamic–pituitary–adrenal (HPA) axis resulting in the release of adrenal glucocorticoids (GC).4 GC exert their actions through their cytoplasmic receptors which translocate to the nucleus and act as a ligand-dependent transcription factor that modulates the expression of glucocorticoid-responsive genes or modifies the activity of other transcription factors such as nuclear factor-κB and activator protein-1. GC affect multiple cell targets and possess numerous immunomodulatory functions: in inflammatory conditions, they suppress the expression of cytokines, chemokines, and adhesion molecules, but they can also have proinflammatory effects such as enhancement of Th2 cytokine production.5 Murine cytomegalovirus (MCMV) infection has been used extensively as a model to study the immune response to the herpes virus CMV, and more particularly the implication of natural killer (NK) cells. It has long been shown that endogenous GC response is protective against cytokine-induced pathology in MCMV infection, but the mechanisms involved are unclear.6

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Fig. 1: Regulation of spleen immunopathology by NK cells during MCMV infection involves HPA-GC-PD-1 axis.

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Authors and Affiliations

  1. Pulmonary Immunity, Institut National de la Santé Et de la Recherche Médicale, U1019, F-59019, Lille, France

    Justine Devulder, Anne Tsicopoulos & Catherine Duez

  2. Institut Pasteur de Lille, Center for Infection and Immunity of Lille, F-59019, Lille, France

    Justine Devulder, Anne Tsicopoulos & Catherine Duez

  3. CNRS UMR 8204, F-59000, Lille, France

    Justine Devulder, Anne Tsicopoulos & Catherine Duez

  4. Univ Lille Nord de France, F-59000, Lille, France

    Justine Devulder, Anne Tsicopoulos & Catherine Duez

  5. Clinique des Maladies Respiratoires et Centre Hospitalier Régional et Universitaire de Lille, 59037, Lille, France

    Anne Tsicopoulos

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  1. Justine Devulder
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Correspondence to Catherine Duez.

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Devulder, J., Tsicopoulos, A. & Duez, C. Neuroendocrine control of natural killer cell function through the checkpoint molecule PD-1. Cell Mol Immunol 16, 109–111 (2019). https://doi.org/10.1038/s41423-018-0180-2

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