Low Expression of T-cell Co-stimulatory Molecules in Bone Marrow-Derived Dendritic Cells in a Mouse Model of Chronic Respiratory Infection with Pseudomonas Aeruginosa

Abstract

Pseudomonas (P.) aeruginosa frequently colonizes the respiratory tract of patients with chronic respiratory tract infections such as diffuse panbronchiolitis (DPB). The number of dendritic cells (DCs) that play a central role in immune functions as antigen-presenting cells is reportedly increased in the bronchiolar tissues of patients with DPB. However, the functions of DCs in chronic P. aeruginosa respiratory tract infection have not been defined. Here, we assessed the functions of DCs and the effect of macrolide antibiotics that are therapeutic agents for DPB, in a murine model of DPB caused by P. aeruginosa. Mice were intubated with either P. aeruginosa- or saline-precoated tubes for 80 days. Thereafter, the expression of T-cell co-stimulatory molecules (CD40, CD80, and CD86) and cytokine secretion (interleukin (IL)-10, IL-6, IL-12p40, and tumor necrosis factor (TNF)-alpha) on bone marrow-derived DCs stimulated by lipopolysaccharide were examined by flow cytometry and enzyme-linked immunosorbent assays. The expression of co-stimulatory molecules was significantly decreased in mice infected with P. aeruginosa compared to the saline-treated control mice, but production of these cytokines did not significantly differ between the two groups. Pretreatment with clarithromycin ex vivo decreased CD40 expression on DCs obtained from P. aeruginosa-infected mice and also decreased the production of IL-6, IL-12p40 and TNF-alpha by DCs. These findings suggest that chronic P. aeruginosa infection alters DC functions and that macrolides function as anti-inflammatory agents by modulating the functions of DCs in chronic P. aeruginosa infection.