In vitro neutralization of tumor necrosis factor-alpha during Chlamydia pneumoniae infection impairs dendritic cells...

Dendritic cells (DCs) produce tumor necrosis factor (TNF)-alpha upon infection and contribute in various ways to defense against pathogenic agents. Several biological agents have been designed to inhibit TNF-alpha activity. However, the use of these inhibitors has been associated with an increased rate of certain opportunistic infections. To study the effect of TNF-alpha inhibition, human monocyte-derived DCs were infected with Chlamydia pneumoniae. TNF-alpha was neutralized by adalimumab, a human anti-TNF-alpha monoclonal antibody. Chlamydiae induced the maturation of DC as determined by flow cytometry and quantitative real-time PCR. However, DC maturation was impaired in the presence of adalimumab. Moreover, neutralization of TNF-alpha resulted in a significant increase of infectious progeny, 16S rRNA gene copy number and development of larger inclusions consisting of different stages of chlamydial development. Additionally, chlamydial infection induced secretion of cytokines/chemokines, which were downregulated by adalimumab treatment. Our data reveal an indirect effect on maturation of DC by C. pneumoniae and that maturation is crucial for the restriction of chlamydial development. The results also demonstrate an increase in infectious progeny after TNF-alpha inhibition, suggesting a contribution of TNF-alpha produced by DCs to chlamydial growth arrest. These data suggest a possible mechanism by which TNF-alpha inhibition enhances the risk of intracellular infections.