Rationale: Chlamydia pneumoniae (Cpn) infection may play a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Few data are available comparing persistent and acute infection of this pathogen in the human respiratory tract. Objectives: To study Cpn - induced innate immune responses in lung tissue from COPD patients and controls ex vivo and in vitro. Methods: Cpn detection was done by nested-PCR, in situ hybridization and immunohistochemistry ex vivo in unstimulated tissue and in vitro using an acute Cpn infection model. As main endpoints for the assessment of early cellular responses nuclear factor-kappa B(NF)- B activation and CXC chemokine ligand(CXCL)-8 expression were evaluated. The role of Toll-like receptors (TLRs) as recognition molecules in Cpn-induced innate responses was tested by blocking experiments. Measurements and main results: 15% of COPD patients were chronically infected with Cpn in contrast to 0% of controls (p< 0.05). There were no differences in CXCL-8 and NF-B expression between infected and non-infected COPD tissue ex vivo. In contrast, acute in vitro infection induced an intense innate immune response including upregulation of TLR2. Blocking experiments demonstrated the predominant role of TLR2 in induction of the early immune response whereas no influence on chlamydial infection rates was observed. Conclusions: Acute in vitro infection of human lung tissue with Cpn elicited a marked innate response via TLR2 whereas chronic chlamydial infection in COPD patients was not associated with enhanced cellular activation. These findings suggest different roles of Cpn during acute and chronic stages of pulmonary infection.