Disparate innate immune responses to persistent and acute Chlamydia pneumoniae infection in chronic obstructive pulmonary disease.
BACKGROUND
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.


OBJECTIVE
To study Cpn-induced innate immune responses in lung tissue from patients with COPD and control subjects ex vivo and in vitro.


METHODS
Cpn detection was done by nested polymerase chain reaction, 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 (NF)-kappaB 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.


RESULTS
Fifteen percent of patients with COPD were chronically infected with Cpn in contrast to 0% of control subjects (p < 0.05). There were no differences in CXCL-8 and NF-kappaB expression between infected and noninfected COPD tissue ex vivo. In contrast, acute in vitro infection induced an intense innate immune response including up-regulation 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 patients with COPD was not associated with enhanced cellular activation. These findings suggest different roles of Cpn during acute and chronic stages of pulmonary infection.
Droemann
Daniel
D
Medical Clinic, Research Center Borstel, Parkallee 35, D-23845 Borstel, Germany. ddroemann@fz-borstel.de
Rupp
Jan
J
Goldmann
Torsten
T
Uhlig
Ulrike
U
Branscheid
Detlev
D
Vollmer
Ekkehard
E
Kujath
Peter
P
Zabel
Peter
P
Dalhoff
Klaus
K
D016022:Case-Control Studies; D023521:Chlamydophila Infections / Q000150:complications* / Q000175:diagnosis / Q000378:metabolism; D016993:Chlamydophila pneumoniae; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D012333:RNA, Messenger / Q000378:metabolism; D046509:Tissue Culture Techniques; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism
C508606:CXCL8 protein, human; D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger; D051193:Toll-Like Receptors