title: 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-alpha antibody infliximab, we further demonstrate in vitro that IDO induction is TNF-alpha dependent. Repression of IDO therefore might result in exacerbation of granulomatous diseases observed during anti-TNF-alpha 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.affiliation: Molecular Tumor Biology and Tumor Immunology at the Clinic I for Internal Medicine, University of Cologne, Cologne, Germany.
authors.forename: Alexey
authors.initials: A
authors.lastname: Popov
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Abdullah
authors.forename: Claudia
authors.initials: C
authors.lastname: Wickenhauser
authors.forename: Tomo
authors.initials: T
authors.lastname: Saric
authors.forename: Julia
authors.initials: J
authors.lastname: Driesen
authors.forename: Franz-Georg
authors.initials: FG
authors.lastname: Hanisch
authors.forename: Eugen
authors.initials: E
authors.lastname: Domann
authors.forename: Emma Lloyd
authors.initials: EL
authors.lastname: Raven
authors.forename: Oliver
authors.initials: O
authors.lastname: Dehus
authors.forename: Corinna
authors.initials: C
authors.lastname: Hermann
authors.forename: Daniela
authors.initials: D
authors.lastname: Eggle
authors.forename: Svenja
authors.initials: S
authors.lastname: Debey
authors.forename: Trinad
authors.initials: T
authors.lastname: Chakraborty
authors.forename: Martin
authors.initials: M
authors.lastname: Krönke
authors.forename: Olaf
authors.initials: O
authors.lastname: Utermöhlen
authors.forename: Joachim L
authors.initials: JL
authors.lastname: Schultze
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000235:genetics; D006099:Granuloma / Q000235:genetics / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics* / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D016256:Lewis X Antigen / Q000032:analysis; D008089:Listeria monocytogenes / Q000254:growth & development*; D008088:Listeriosis / Q000235:genetics / Q000378:metabolism / Q000382:microbiology; D008264:Macrophages / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D009418:S100 Proteins / Q000032:analysis; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D017252:CD3 Complex; D051546:Cyclooxygenase 2; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma; D016256:Lewis X Antigen; D008565:Membrane Proteins; D009418:S100 Proteins; D014409:Tumor Necrosis Factor-alpha; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C496540:PTGS2 protein, human