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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, CD / analysis
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Antigens, Differentiation, Myelomonocytic / analysis
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CD3 Complex / analysis
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Cells, Cultured
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Cyclooxygenase 2 / genetics
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Cyclooxygenase 2 / metabolism
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Dendritic Cells / cytology
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Dendritic Cells / metabolism*
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Dendritic Cells / microbiology
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Enzyme-Linked Immunosorbent Assay
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Gene Expression / genetics
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Granuloma / genetics
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Granuloma / metabolism
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Granuloma / microbiology
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Humans
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Immunoblotting
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Immunohistochemistry
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Indoleamine-Pyrrole 2,3,-Dioxygenase / genetics*
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Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
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Interferon-gamma / genetics
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Interferon-gamma / metabolism
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Lewis X Antigen / analysis
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Listeria monocytogenes / growth & development*
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Listeriosis / genetics
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Listeriosis / metabolism
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Listeriosis / microbiology
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Macrophages / cytology
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Macrophages / metabolism
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Macrophages / microbiology
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Oligonucleotide Array Sequence Analysis
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S100 Proteins / analysis
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Time Factors
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Antigens, CD
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Antigens, Differentiation, Myelomonocytic
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CD3 Complex
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CD68 antigen, human
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Indoleamine-Pyrrole 2,3,-Dioxygenase
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Lewis X Antigen
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Membrane Proteins
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S100 Proteins
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Tumor Necrosis Factor-alpha
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Interferon-gamma
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Cyclooxygenase 2
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PTGS2 protein, human