title: Divergent pro-inflammatory profile of human dendritic cells in response to commensal and pathogenic bacteria associated with the airway microbiota.
abstract: Recent studies using culture-independent methods have characterized the human airway microbiota and report microbial communities distinct from other body sites. Changes in these airway bacterial communities appear to be associated with inflammatory lung disease, yet the pro-inflammatory properties of individual bacterial species are unknown. In this study, we compared the immune stimulatory capacity on human monocyte-derived dendritic cells (DCs) of selected airway commensal and pathogenic bacteria predominantly associated with lungs of asthma or COPD patients (pathogenic Haemophillus spp. and Moraxella spp.), healthy lungs (commensal Prevotella spp.) or both (commensal Veillonella spp. and Actinomyces spp.). All bacteria were found to induce activation of DCs as demonstrated by similar induction of CD83, CD40 and CD86 surface expression. However, asthma and COPD-associated pathogenic bacteria provoked a 3-5 fold higher production of IL-23, IL-12p70 and IL-10 cytokines compared to the commensal bacteria. Based on the differential cytokine production profiles, the studied airway bacteria could be segregated into three groups (Haemophilus spp. and Moraxella spp. vs. Prevotella spp. and Veillonella spp. vs. Actinomyces spp.) reflecting their pro-inflammatory effects on DCs. Co-culture experiments found that Prevotella spp. were able to reduce Haemophillus influenzae-induced IL-12p70 in DCs, whereas no effect was observed on IL-23 and IL-10 production. This study demonstrates intrinsic differences in DC stimulating properties of bacteria associated with the airway microbiota.
authors.affiliation: Systems Biology of Immune Regulation, Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark. jeml@bio.dtu.dk
authors.forename: Jeppe Madura
authors.initials: JM
authors.lastname: Larsen
authors.forename: Daniel Bisgaard
authors.initials: DB
authors.lastname: Steen-Jensen
authors.forename: Janne Marie
authors.initials: JM
authors.lastname: Laursen
authors.forename: Jonas Nørskov
authors.initials: JN
authors.lastname: Søndergaard
authors.forename: Hanieh Sadat
authors.initials: HS
authors.lastname: Musavian
authors.forename: Tariq Mahmood
authors.initials: TM
authors.lastname: Butt
authors.forename: Susanne
authors.initials: S
authors.lastname: Brix
mesh_terms: D001419:Bacteria / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D006190:Haemophilus / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D054892:Metagenome / Q000276:immunology*; D010802:Phylogeny; D018720:Prevotella / Q000276:immunology; D025341:Principal Component Analysis; D013045:Species Specificity; D014019:Tissue Donors
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators