Endogenous glucocorticoids control host resistance to viral infection through the tissue-specific regulation of PD-1 expression on NK cells. - Aix-Marseille Université Access content directly
Journal Articles Nature Immunology Year : 2018

Endogenous glucocorticoids control host resistance to viral infection through the tissue-specific regulation of PD-1 expression on NK cells.

Abstract

Controlling the balance between immunity and immunopathology is crucial for host resistance to pathogens. After infection, activation of the hypothalamic-pituitary-adrenal (HPA) axis leads to the production of glucocorticoids. However, the pleiotropic effects of these steroid hormones make it difficult to delineate their precise role(s) in vivo. Here we found that the regulation of natural killer (NK) cell function by the glucocorticoid receptor (GR) was required for host survival after infection with mouse cytomegalovirus (MCMV). Mechanistically, endogenous glucocorticoids produced shortly after infection induced selective and tissue-specific expression of the checkpoint receptor PD-1 on NK cells. This glucocorticoid-PD-1 pathway limited production of the cytokine IFN-gamma by spleen NK cells, which prevented immunopathology. Notably, this regulation did not compromise viral clearance. Thus, the fine tuning of NK cell functions by the HPA axis preserved tissue integrity without impairing pathogen elimination, which reveals a novel aspect of neuroimmune regulation.

Domains

Immunology

Dates and versions

hal-02086848 , version 1 (01-04-2019)

Identifiers

Cite

Linda Quatrini, Elisabeth Wieduwild, Bertrand Escaliere, Jessica Filtjens, Lionel Chasson, et al.. Endogenous glucocorticoids control host resistance to viral infection through the tissue-specific regulation of PD-1 expression on NK cells.. Nature Immunology, 2018, 19 (9), pp.954--962. ⟨10.1038/s41590-018-0185-0⟩. ⟨hal-02086848⟩
50 View
0 Download

Altmetric

Share

Gmail Facebook X LinkedIn More