Indoleamine 2,3-dioxygenase-expressing dendritic cells form suppurative granulomas following Listeria monocytogenes infection.
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.
Popov
Alexey
A
Molecular Tumor Biology and Tumor Immunology at the Clinic I for Internal Medicine, University of Cologne, Cologne, Germany.
Abdullah
Zeinab
Z
Wickenhauser
Claudia
C
Saric
Tomo
T
Driesen
Julia
J
Hanisch
Franz-Georg
FG
Domann
Eugen
E
Raven
Emma Lloyd
EL
Dehus
Oliver
O
Hermann
Corinna
C
Eggle
Daniela
D
Debey
Svenja
S
Chakraborty
Trinad
T
Krönke
Martin
M
Utermöhlen
Olaf
O
Schultze
Joachim L
JL
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
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