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

Overall transcriptional changes in human DCs infected with L. monocytogenes.

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Overall transcriptional changes in human DCs infected with L. monocytoge...
(A) Unsupervised hierarchical clustering analysis of immDCs infected with L. monocytogenes (L.m.) for 2 hours or 6 hours or control (Con) mock-infected DCs, cultured at the same conditions for 2 hours or 6 hours. Affymetrix raw data were normalized using dChip, and a list of 1189 genes with high variability across the data set (0.5 < SD/mean < 10) was used for hierarchical clustering in dChip. (B) Visualization using GeneSpring software of the most significantly changed genes after infection with L. monocytogenes. A total of 902 transcripts were defined with dChip as significantly changed at either time point; filtering criteria are described in detail in Methods. These significantly changed genes were ordered according to the temporal pattern of expression changes. Immediate-response genes are defined as being either up- or downregulated at the 2-hour time point but not at the 6-hour time point. Immediate-early response genes are characterized by upregulated or downregulated genes at both time points, and early response genes are regulated only at 6 hours. Expression values were normalized and color coded with upregulated genes in red and downregulated genes in blue. Each colored curve represents an expression pattern of a single gene; each vertical line represents 1 sample as indicated at the bottom of the figure. Detailed gene information is provided in Supplemental Table 2.