title: Activation of pulmonary and lymph node dendritic cells during chronic Pseudomonas aeruginosa lung infection in mice.
abstract: The majority of cystic fibrosis (CF) patients acquire chronic Pseudomonas aeruginosa lung infection, resulting in increased mortality and morbidity. The chronic P. aeruginosa lung infection is characterized by bacteria growing in biofilm surrounded by polymorphonuclear neutrophils (PMNs). However, the infection is not eradicated and the inflammatory response leads to gradual degradation of the lung tissue. In CF patients, a Th2-dominated adaptive immune response with a pronounced antibody response is correlated with poorer outcome. Dendritic cells (DCs) are crucial in bridging the innate immune system with the adaptive immune response. Once activated, the DCs deliver a set of signals to uncommitted T cells that induce development, such as expansion of regulatory T cells and polarization of Th1, Th2 or Th17 subsets. In this study, we characterized DCs in lungs and regional lymph nodes in BALB/c mice infected using intratracheal installation of P. aeruginosa embedded in seaweed alginate in the lungs. A significantly elevated concentration of DCs was detected earlier in the lungs than in the regional lymph nodes. To evaluate whether the chronic P. aeruginosa lung infection leads to activation of DCs, costimulatory molecules CD80 and CD86 were analyzed. During infection, the DCs showed significant elevation of CD80 and CD86 expression in both the lungs and the regional lymph nodes. Interestingly, the percentage of CD86-positive cells was significantly higher than the percentage of CD80-positive cells in the lymph nodes. In addition, cytokine production from Lipopolysaccharides (LPS)-stimulated DCs was analyzed demonstrating elevated production of IL-6, IL-10 and IL-12. However, production of IL-12 was suppressed earlier than IL-6 and IL-10. These results support that DCs are involved in skewing of the Th1/Th2 balance in CF and may be a possible treatment target.
authors.affiliation: Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Dina Silke Malling
authors.initials: DS
authors.lastname: Damlund
authors.affiliation: Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Christophersen
authors.affiliation: Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Peter Østrup
authors.initials: PØ
authors.lastname: Jensen
authors.affiliation: Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.|Department of International Health, Immunology and Microbiology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Alhede
authors.affiliation: Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Høiby
authors.affiliation: Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Moser
mesh_terms: D000818:Animals; D018122:B7-1 Antigen / Q000032:analysis; D051940:B7-2 Antigen / Q000032:analysis; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000737:chemistry / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D008168:Lung / Q000473:pathology*; D008198:Lymph Nodes / Q000276:immunology*; D008807:Mice, Inbred BALB C; D018410:Pneumonia, Bacterial / Q000473:pathology*; D011552:Pseudomonas Infections / Q000473:pathology*; D011550:Pseudomonas aeruginosa / Q000276:immunology*
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D016207:Cytokines
keywords: Pseudomonas aeruginosa; cystic fibrosis; dendritic cells; lung infection