title: Chlamydia pneumoniae modulates human monocyte-derived dendritic cells functions driving the induction of a Type 1/Type 17 inflammatory response.
abstract: Chlamydia pneumoniae is a respiratory pathogen involved in the onset of chronic inflammatory pathologies. Dendritic cells (DC), are major players in spreading of C. pneumoniae from the lungs, a crucial step leading to disseminated infections. Less is known concerning modulation of DC functions consequent to encounter with the bacterium. In order to address this aspect, human monocyte-derived (MD)DC were infected with C. pneumoniae. After internalization bacterial counts increased in MDDC, as well as the expression of CPn1046, a gene involved in bacterial metabolism, with a peak 48 h after the infection. Infected MDDC switched to the mature stage, produced IL-12p70, IL-1β, IL-6, and IL-10, and drove a mixed Type 1/Type 17 polarization. Intracellular pathways triggered by C. pneumoniae involved Toll-like receptor (TLR) 2. Indeed, TLR2 was activated by C. pneumoniae in transfected HEK 293 cells, and C. pneumoniae-mediated phosphorylation of ERK1/2 was inhibited by an anti-TLR2 antibody in MDDC. When an ERK1/2 inhibitor was used, IL-12p70 and IL-10 release by MDDC was reduced and T cell polarization shifted towards a Type 2 profile. Overall, our findings unveiled the role played by TLR2 and ERK1/2 induced by C. pneumoniae to affect DC functions in a way that contributes to a Type 1/Type 17 pro-inflammatory response.
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Flego
authors.forename: Manuela
authors.initials: M
authors.lastname: Bianco
authors.forename: Adriano
authors.initials: A
authors.lastname: Quattrini
authors.forename: Fabiola
authors.initials: F
authors.lastname: Mancini
authors.forename: Maria
authors.initials: M
authors.lastname: Carollo
authors.forename: Ilaria
authors.initials: I
authors.lastname: Schiavoni
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ciervo
authors.forename: Clara M
authors.initials: CM
authors.lastname: Ausiello
authors.forename: Giorgio
authors.initials: G
authors.lastname: Fedele
mesh_terms: D000906:Antibodies / Q000276:immunology; D017209:Apoptosis; D058491:Bacterial Load; D016764:Cell Polarity; D002478:Cells, Cultured; D023521:Chlamydophila Infections / Q000276:immunology / Q000382:microbiology; D016993:Chlamydophila pneumoniae / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000382:microbiology*; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology*; D018664:Interleukin-12 / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology*; D008213:Lymphocyte Activation; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000276:immunology; D009000:Monocytes / Q000166:cytology* / Q000276:immunology; D010587:Phagocytosis; D010766:Phosphorylation; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D013997:Time Factors; D051195:Toll-Like Receptor 2 / Q000276:immunology; D014162:Transfection
chemical_list: D000906:Antibodies; D005419:Flavonoids; D007375:Interleukin-1; D020381:Interleukin-17; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D018664:Interleukin-12; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one