Steroid-induced deficiency of mucosal-associated invariant T cells in the chronic Obstructive Pulmonary Disease lung: Implications for Nontypeable Haemophilus influenzae Infection

Abstract

Rationale: Mucosal associated invariant T (MAIT) cells are a recently-described, abundant, pro-inflammatory T cell subset with unknown roles in pulmonary immunity. Non-typeable Haemophilus influenzae (NTHi) is the leading bacterial pathogen during COPD exacerbations and a plausible target for MAIT cells.

Objectives: To investigate whether MAIT cells respond to NTHi and the effects of inhaled corticosteroids on their frequency and function in COPD.

Methods: 11 participants with COPD receiving inhaled corticosteroids (ICS), 8 with steroid-naïve COPD and 21 healthy controls underwent phlebotomy, sputum induction, bronchoalveolar-lavage and endobronchial biopsy. Pulmonary and monocyte-derived macrophages were cultured in vitro with NTHi.

Measurements: Frequencies of Va7.2+CD161+ MAIT cells, surface expression of MHC-related protein 1 (MR1) and intracellular IFN-y expression were measured by flow cytometry.

Main Results: MAIT cell frequencies were reduced in peripheral blood in ICS-treated COPD (median 0.38% (IQR, 0.25-0.96) compared with health (1.8% (IQR, 1.4-2.5), P=0.001)) or steroid-naïve COPD (1.8% (1.2-2.3), P=0.04). MAIT cells were reduced in bronchial biopsies in steroid-treated COPD (0.73% (0.46-1.3)) compared with health (4.0% (1.6-5.0), P=0.02). Co-culture of live NTHi increased macrophage surface expression of MR1 and induced IFN-? from CD4 cells and CD8 cells, but most potently from MAIT cells (median IFN-y positive frequencies 2.9%, 8.6% and 27.6% respectively). In vitro fluticasone and budesonide reduced MR1 surface expression 2-fold and decreased NTHi-induced IFN-y secretion 8-fold.

Conclusions: MAIT cells are deficient in blood and bronchial tissue in steroid-treated, but not steroid-naïve COPD. NTHi constitutes a target for pulmonary MAIT cell immune responses, which are significantly impaired by corticosteroids.

More information

Identifiers

ORCID for Ratko Djukanovic: orcid.org/0000-0001-6039-5612

ORCID for Karl J Staples: orcid.org/0000-0003-3844-6457

Catalogue record

Export record

Altmetrics