Indoleamine 2,3-dioxygenase–expressing dendritic cells form suppurative granulomas following Listeria monocytogenes infection
Alexey Popov, … , Olaf Utermöhlen, Joachim L. Schultze
Alexey Popov, … , Olaf Utermöhlen, Joachim L. Schultze
Published December 1, 2006
Citation Information: J Clin Invest. 2006;116(12):3160-3170. https://doi.org/10.1172/JCI28996.
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Research Article Immunology

Indoleamine 2,3-dioxygenase–expressing dendritic cells form suppurative granulomas following Listeria monocytogenes infection

Abstract

Control of pathogens by formation of abscesses and granulomas is a major strategy of the innate immune system, especially when effector mechanisms of adaptive immunity are insufficient. We show in human listeriosis that DCs expressing indoleamine 2,3-dioxygenase (IDO), together with macrophages, are major cellular components of suppurative granulomas in vivo. Induction of IDO by DCs is a cell-autonomous response to Listeria monocytogenes infection and was also observed in other granulomatous infections with intracellular bacteria, such as Bartonella henselae. Reporting on our use of the clinically applied anti–TNF-α antibody infliximab, we further demonstrate in vitro that IDO induction is TNF-α dependent. Repression of IDO therefore might result in exacerbation of granulomatous diseases observed during anti–TNF-α therapy. These findings place IDO+ DCs not only at the intersection of innate and adaptive immunity but also at the forefront of bacterial containment in granulomatous infections.

Authors

Alexey Popov, Zeinab Abdullah, Claudia Wickenhauser, Tomo Saric, Julia Driesen, Franz-Georg Hanisch, Eugen Domann, Emma Lloyd Raven, Oliver Dehus, Corinna Hermann, Daniela Eggle, Svenja Debey, Trinad Chakraborty, Martin Krönke, Olaf Utermöhlen, Joachim L. Schultze

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Figure 3

IDO is expressed on transcriptional and functional levels in human DCs infected with L. monocytogenes.

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IDO is expressed on transcriptional and functional levels in human DCs i...
(A) Time kinetic of IDO mRNA expression was assessed by quantitative real-time PCR. Expression of β-2 microglobulin (B2M) was used as a housekeeping gene control. Shown here are IDO expression profiles (normalized to B2M expression) in DC cultures derived from 3 different donors. Samples after L. monocytogenes infection are represented by filled symbols, the corresponding control samples by open symbols. (B) Protein expression of IDO and β-actin was assessed by immunoblotting after L. monocytogenes infection. Results of 1 representative experiment out of 6 are shown. rhIDO was used as a positive control. (C) Tryptophan depletion by enzymatically active IDO in cell supernatants was assessed by reverse-phase HPLC. Shown here is the reduction of tryptophan after 6, 12, or 24 hours in DC culture supernatants relative to tryptophan concentrations measured in DC medium alone. Mean ± SD of 3 independent experiments is shown. Asterisks highlight statistically significant comparisons (*P < 0.05, **P < 0.00001). (D) Kynurenine accumulation at the same time points was assessed using a photometric assay. Shown here are mean ± SD of 3 independent experiments. Asterisks highlight statistically significant comparison (***P < 0.01). (E) Macrophages (Mf) and DCs were differentiated from monocytes and infected with wild-type L. monocytogenes. After 24 hours, IDO protein expression was assessed by immunoblotting and analyzed quantitatively respective to β-actin expression. Representative Western blot and mean ± SD of 3 independent experiments are shown. Asterisks highlight statistically significant comparison (***P < 0.01).