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 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.
Abstract
NK cells from severe asthma patients exhibit decreased activation, cytotoxic capacity and IFN-γ production after in vitro stimulation with rhinovirus RV-A9, in comparison to healthy donors. Exhausted phenotype is associated to increased Tim-3 expression. http://bit.ly/2UFjtdc
Footnotes
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Conflict of interest: J. Devulder has a patent EP18306287.6 issued to INSERM.
Conflict of interest: C. Chenivesse has a patent EP18306287.6 issued to INSERM.
Conflict of interest: V. Ledroit has nothing to disclose.
Conflict of interest: S. Fry has nothing to disclose.
Conflict of interest: P-E. Lobert has nothing to disclose.
Conflict of interest: D. Hober has nothing to disclose.
Conflict of interest: A. Tsicopoulos has nothing to disclose.
Conflict of interest: C. Duez has a patent EP18306287.6 issued to INSERM.
Support statement: This work was supported by INSERM. J. Devulder is supported by a grant from Ministère de l'Enseignement supérieur, de la Recherche et de l'Innovation, and by a grant from Fonds de Recherche en Santé Respiratoire (FRSR). Funding information for this article has been deposited with the Crossref Funder Registry.
- Received December 26, 2018.
- Accepted February 3, 2020.
- Copyright ©ERS 2020