Effect of lipoteichoic acid on IL-2 and IL-5 release from T lymphocytes in asthma and COPD

Susceptibility to infections with gram-positive bacteria, which are an important trigger of exacerbations, is increased in COPD and asthma. Unraveling the underlying mechanisms may help developing therapeutic strategies to reduce exacerbation rates. The aim of this study was to evaluate the effects of lipoteichoic acid (LTA), a danger signal from gram-positive bacteria, on T cell cytokines related to bacterial infection defense in COPD and asthma.T cell populations within peripheral blood mononuclear cells (PBMCs) were ex-vivo activated towards TH2/TC2 subtypes and subsequently stimulated with LTA. IL-2 and IL-5 concentrations in cell culture supernatants were measured by ELISA comparative between non-smokers (NS), current smokers without airflow limitation (S), smokers with moderate to severe COPD and mild to moderate asthmatics (A) (each n = 10).IL-2 and IL-5 baseline levels were without differences between the cohorts. After T cell activation, IL-2 and IL-5 releases were increased in all cohorts, however, for IL-2 this increase was significantly higher in S and by trend in COPD compared to the other groups. LTA time-dependently suppressed IL-2 release in NS, S and COPD but not in A. LTA reduced IL-5 release in COPD and A but not in NS and S.Summarized, LTA reduces TH2/TC2 cytokines indicating immunosuppressive effects, which are dysregulated in COPD and asthma. This implies a misguided response to gram-positive bacterial infections, which might help to explain the increased susceptibility to bacterial infections in COPD and asthma.

► Bacterial infections induce exacerbations in asthma and COPD ► Bacterial lipoteichoic acid (LTA) suppresses IL-2 and IL-5 in Tc2 cells ► LTA interaction with T cells requires accessory cells ► T cell response to LTA is dysregulated in asthma and COPD ► This might explain the increased bacterial infection susceptibility in asthma/COPD