Justine Devulder, Cécile Chenivesse, Valérie Ledroit, Stéphanie Fry, Pierre-Emmanuel Lobert, Didier Hober, Anne Tsicopoulos, Catherine Duez
European Respiratory Journal 2020; DOI: 10.1183/13993003.02422-2018
Abstract
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 IFN-γ expression were analysed. NK cells from severe asthma patients were less cytotoxic than those from healthy donors in response to TLR3, TLR7/8 or RV-A9 but not in response to RV-2 stimulation. Furthermore, when cultured with 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.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: Dr DEVULDER reports In addition, Dr DEVULDER has a patent EP18306287.6 issued to INSERM.
Conflict of interest: Dr CHENIVESSE reports In addition, Dr CHENIVESSE has a patent EP18306287.6 issued to INSERM.
Conflict of interest: Dr LEDROIT has nothing to disclose.
Conflict of interest: Dr FRY has nothing to disclose.
Conflict of interest: Dr LOBERT has nothing to disclose.
Conflict of interest: Dr HOBER has nothing to disclose.
Conflict of interest: Dr TSICOPOULOS has nothing to disclose.
Conflict of interest: Dr DUEZ reports In addition, Dr DUEZ has a patent EP18306287.6 issued to INSERM.
- Received December 26, 2018.
- Accepted February 3, 2020.
- Copyright ©ERS 2020
