In vitro neutralization of tumor necrosis factor-a during Chlamydia pneumoniae infection impairs dendritic cells maturation/function and increases chlamydial progeny

• Published in: FEMS immunology and medical microbiology Vol. 55; no. 2; pp. 215 - 225
• Main Authors: Njau, Florence, Wittkop, Ulrike, Rohde, Manfred, Haller, Hermann, Klos, Andreas, Wagner, Annette Doris
• Format: Journal Article
• Language: English
• Published: 01-03-2009
• Subjects: Chlamydophila pneumoniae
• ISSN: 0928-8244; 1574-695X
• DOI: 10.1111/j.1574-695X.2008.00512.x

AbstractDendritic cells (DCs) produce tumor necrosis factor (TNF)-a upon infection and contribute in various ways to defense against pathogenic agents. Several biological agents have been designed to inhibit TNF-a activity. However, the use of these inhibitors has been associated with an increased rate of certain opportunistic infections. To study the effect of TNF-a inhibition, human monocyte-derived DCs were infected with Chlamydia pneumoniae. TNF-a was neutralized by adalimumab, a human anti-TNF-a 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-a 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-a inhibition, suggesting a contribution of TNF-a produced by DCs to chlamydial growth arrest. These data suggest a possible mechanism by which TNF-a inhibition enhances the risk of intracellular infections.