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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

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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 4

Regulation of genes and proteins shown to be associated with induction of IDO.

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Regulation of genes and proteins shown to be associated with induction o...
(A) Heat map showing fold changes of gene transcription for type I and II IFNs, TNF-α, and PTGS2 (COX-2) as well as the corresponding receptors. Fold changes were calculated for each individual sample pair (control DCs versus infected DCs from a matching donor at the respective time point) and color coded (blue, downregulated; white, unchanged; and red, upregulated genes); scale of fold changes ranged from –5.19 FC to +136.48 FC (Supplemental Table 3). (B) Protein expression of TNF-α in supernatants from immDCs either infected with L. monocytogenes (+) or not infected (–) and subsequently cultured for up to 24 hours. Expression of TNF-α was assessed by ELISA. Shown here are mean ± SD derived from 4 different donors. Asterisks highlight statistically significant comparisons (*P < 0.05; **P < 0.01). (C) At the same time points as in B, DCs were harvested and subsequently lysed to assess protein expression of COX-2 and β-actin by immunoblotting. Results of 1 representative experiment out of 6 are shown. (D) To assess the function of COX-2 in DCs infected with L. monocytogenes (+) or control DCs (–), stable PGE metabolites (PGEM) were measured in DC supernatants by EIA at the indicated time points (n = 2). Asterisks highlight statistically significant comparisons (**P < 0.01). (E) Expression of IFN-γ was assessed by ELISA. Shown here are mean ± SD derived from 4 different donors. Asterisks highlight statistically significant comparisons (*P < 0.05).

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