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
View: Text | PDF
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

×

Figure 1

Human DCs in L. monocytogenes infection.

Options: View larger image (or click on image) Download as PowerPoint
Human DCs in L. monocytogenes infection. (A) Histomorpho...
(A) Histomorphology of lymph node sections from a patient with suppurative granulomatous listeriosis. H&E staining of a sample slide with prominent ring-wall formation of histiocytoid cells around suppurative granulomas in listeriosis. Magnification, ×100 and ×400 (H&E panels). Photographs of immunohistochemical staining with CD20, CD3, CD15, CD68, S100, CD11c, and IDO are shown. Magnification, ×250. One out of 3 comparable cases is depicted here. (B) Immunofluorescence of the same patient samples described above. S100 and CD68 were combined to distinguish between DCs and macrophages. S100 and CD11c were combined to determine a myeloid origin of the S100+ DCs. As a second marker for macrophages, double staining with CD68 and CD11c was performed. To assess expression of IDO by myeloid cells, DCs, and macrophages, analysis of IDO was combined with S100, CD11c, or CD68. One out of 3 cases is presented. Magnification, ×250. In each lower-left corner, an enlarged section of the photo is shown for more detail (magnification, ×2500). (C) Confocal microscopy (Olympus FluoView FV1000 Confocal Microscope) clearly confirms the colocalization of IDO with S100 and CD68. Magnification, ×2500.