Mechanisms of impaired anti-bacterial Th1 responses in patients with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is the most common respiratory disorder worldwide. Some COPD patients experience acute exacerbation of COPD (AECOPD) which are associated with pulmonary bacterial infections and accelerated disease progression. We hypothesised that the expression of co-inhibitory molecules on T-cells (CTLA-4, PD-1 and CD39) are increased in COPD patients and so limit protective T-helper type 1 (Th1) responses.We investigated expression of T-cell CTLA-4, PD-1, CD39 and Foxp3 in resected lung washout samples from COPD and non-COPD subjects by flow cytometry. Phagocytosis by airway monocytes was measured using flow cytometry with non-typeable Haemophilus influenzae (NTHI) labelled with the novel fluorogenic dye, pHrodo that fluoresces brightly in acidic compartments. Peripheral blood mononuclear cells (PBMC) from a cohort of AECOPD, stable COPD (sCOPD) and healthy controls were challenged with live NTHI and the level of Th1 cytokine (IFN) was measured.Airway CD4+ T-cells expressing CD39, PD-1 or Foxp3 and CD8+ T-cells expressing CD39 were increased in COPD patients compared to non-COPD controls. Using this assay, airway monocytes from COPD patients were less phagocytic than non-COPD controls. The intracellular persistence of NTHI in PBMC was also more common in sCOPD patients than controls suggesting impaired bacterial clearance. PBMC from AECOPD patients produced lower levels of IFN than those from sCOPD patients or healthy controls (p=0.03).Impaired...

Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Tan, D., Singh, D., Walters, H., Wark, P., Moodley, Y. Tags: Allergy and immunology Source Type: research