Restriction of Chlamydia pneumoniae replication in human dendritic cell by activation of indoleamine 2,3-dioxygenase.
Infection with Chlamydia pneumoniae, a human respiratory pathogen, has been associated with various chronic diseases such as asthma and atherosclerosis, possibly because the pathogen can exist in a persistent form. C. pneumoniae persistently infect DCs in a TNF-alpha dependent manner. The present study investigated whether C. pneumoniae infection can induce indoleamine 2,3-dioxygenase (IDO) activity in dendritic cells, and whether the restriction of chlamydial growth in the DCs by TNF-alpha is IDO dependent. Our data indicate that infection of DCs with C. pneumoniae resulted in the induction of IDO expression. Reporting on our use of anti-TNF-alpha antibody adalimumab and varying concentrations of TNF-alpha, we further demonstrate that IDO induction following infection of DCs with C. pneumoniae is TNF-alpha dependent. The anti-chlamydial activity induced by TNF-alpha and the expression of chlamydial 16S rRNA gene, euo, groEL1, ftsk and tal genes were correlated with induction of IDO. Addition of excess amounts of tryptophan to the DC cultures resulted in abrogation of the TNF-alpha-mediated chlamydial growth restriction. These findings suggest that infection of DCs by C. pneumoniae induces production of functional IDO, which subsequently causes depletion of tryptophan. This may represent a potential mechanism for DCs to restrict bacterial growth in chlamydial infections.
Njau
Florence
F
Department of Nephrology, Hannover Medical School, Carl Neuberg Strasse 1, 30625 Hannover, Germany. fnjau@yahoo.com
Geffers
Robert
R
Thalmann
Jessica
J
Haller
Hermann
H
Wagner
Annette Doris
AD
D000068879:Adalimumab; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D048708:Cell Growth Processes / Q000187:drug effects; D023521:Chlamydophila Infections / Q000235:genetics / Q000276:immunology*; D016993:Chlamydophila pneumoniae / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D054884:Host-Pathogen Interactions; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D015203:Reproducibility of Results; D014364:Tryptophan / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001426:Bacterial Proteins; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D014364:Tryptophan; D000068879:Adalimumab