Aberrant anti-viral response of natural killer cells in severe asthma.
Justine DevulderCécile ChenivesseValérie LedroitStéphanie FryPierre-Emmanuel LobertDidier HoberAnne TsicopoulosCatherine DuezPublished in: The European respiratory journal (2020)
Rhinovirus infections are the main cause of asthma exacerbations. As natural killer (NK) cells are important actors of the antiviral innate response, we aimed at evaluating the functions of NK cells from severe asthma patients in response to rhinovirus-like molecules or rhinoviruses.Peripheral blood mononuclear cells from patients with severe asthma and healthy donors were stimulated with pathogen-like molecules or with the rhinoviruses (RV)-A9 and RV-2. NK cell activation, degranulation and interferon (IFN)-γ expression were analysed.NK cells from severe asthma patients were less cytotoxic than those from healthy donors in response to toll-like receptor (TLR)3, TLR7/8 or RV-A9 but not in response to RV-2 stimulation. Furthermore, when cultured with interleukin (IL)-12+IL-15, cytokines which are produced during viral infections, NK cells from patients with severe asthma were less cytotoxic and expressed less IFN-γ than NK cells from healthy donors. NK cells from severe asthmatics exhibited an exhausted phenotype, with an increased expression of the checkpoint molecule Tim-3.Together, our findings indicate that the activation of NK cells from patients with severe asthma may be insufficient during some but not all respiratory infections. The exhausted phenotype may participate in NK cell impairment and aggravation of viral-induced asthma exacerbation in these patients.
Keyphrases
- nk cells
- toll like receptor
- end stage renal disease
- mycobacterium tuberculosis
- immune response
- chronic obstructive pulmonary disease
- ejection fraction
- newly diagnosed
- inflammatory response
- chronic kidney disease
- peritoneal dialysis
- poor prognosis
- prognostic factors
- dendritic cells
- sars cov
- endothelial cells
- cystic fibrosis
- lung function
- long non coding rna
- patient reported outcomes
- nuclear factor
- acute respiratory distress syndrome