Chlamydophila pneumoniae induces a sustained airway hyperresponsiveness and inflammation in mice.
BACKGROUND
It has been reported that Chlamydophila (C.) pneumoniae is involved in the initiation and promotion of asthma and chronic obstructive pulmonary diseases (COPD). Surprisingly, the effect of C. pneumoniae on airway function has never been investigated.


METHODS
In this study, mice were inoculated intranasally with C. pneumoniae (strain AR39) on day 0 and experiments were performed on day 2, 7, 14 and 21.


RESULTS
We found that from day 7, C. pneumoniae infection causes both a sustained airway hyperresponsiveness and an inflammation. Interferon-gamma (IFN-gamma) and macrophage inflammatory chemokine-2 (MIP-2) levels in bronchoalveolar lavage (BAL)-fluid were increased on all experimental days with exception of day 7 where MIP-2 concentrations dropped to control levels. In contrast, tumor necrosis factor-alpha (TNF-alpha) levels were only increased on day 7. From day 7 to 21 epithelial damage and secretory cell hypertrophy was observed. It is suggested that, the inflammatory cells/mediators, the epithelial damage and secretory cell hypertrophy contribute to initiation of airway hyperresponsiveness.


CONCLUSIONS
Our study demonstrates for the first time that C. pneumoniae infection can modify bronchial responsiveness. This has clinical implications, since additional changes in airway responsiveness and inflammation-status induced by this bacterium may worsen and/or provoke breathlessness in asthma and COPD.
Blasi
Francesco
F
Institute of Respiratory Diseases, University of Milan, IRCCS Ospedale Maggiore Fondazione Policlinico-Mangiagalli-Regina Elena, Milano, Italy. francesco.blasi@unimi.it
Aliberti
Stefano
S
Allegra
Luigi
L
Piatti
Gioia
G
Tarsia
Paolo
P
Ossewaarde
Jacobus M
JM
Verweij
Vivienne
V
Nijkamp
Frans P
FP
Folkerts
Gert
G
D000818:Animals; D016535:Bronchial Hyperreactivity / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000382:microbiology; D054426:Chemokine CXCL2 / Q000378:metabolism; D023521:Chlamydophila Infections / Q000150:complications* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D016993:Chlamydophila pneumoniae; D002923:Cilia / Q000382:microbiology / Q000648:ultrastructure; D004195:Disease Models, Animal; D006984:Hypertrophy; D007371:Interferon-gamma / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000382:microbiology* / Q000503:physiopathology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning; D018410:Pneumonia, Bacterial / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology / Q000503:physiopathology; D012129:Respiratory Function Tests; D020545:Respiratory Mucosa / Q000382:microbiology / Q000648:ultrastructure; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma