Restriction of Chlamydia pneumoniae replication in human dendritic cell by activation of indoleamine 2,3-dioxygenase

Abstract 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-α 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-α 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-α antibody adalimumab and varying concentrations of TNF-α, we further demonstrate that IDO induction following infection of DCs with C. pneumoniae is TNF-α dependent. The anti-chlamydial activity induced by TNF-α 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-α-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.