title: 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.
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan. hmukae@med.uoeh-u.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mukae
authors.forename: Kanako
authors.initials: K
authors.lastname: Urabe
authors.forename: Katsunori
authors.initials: K
authors.lastname: Yanagihara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishimoto
authors.forename: Noriho
authors.initials: N
authors.lastname: Sakamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishii
authors.forename: Seiko
authors.initials: S
authors.lastname: Nakayama
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ishimatsu
authors.forename: Koh
authors.initials: K
authors.lastname: Abe
authors.forename: Ryo
authors.initials: R
authors.lastname: Shirai
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D004195:Disease Models, Animal; D018942:Macrolides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D011552:Pseudomonas Infections / Q000150:complications / Q000276:immunology* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000502:physiology*; D012141:Respiratory Tract Infections / Q000150:complications / Q000276:immunology* / Q000382:microbiology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
chemical_list: D000954:Antigens, Surface; D016207:Cytokines; D018942:Macrolides