title: Infection of myeloid dendritic cells with Listeria monocytogenes leads to the suppression of T cell function by multiple inhibitory mechanisms.
abstract: Myeloid dendritic cells (DC) and macrophages play an important role in pathogen sensing and antimicrobial defense. In this study we provide evidence that myeloid DC respond to infection with Listeria monocytogenes with simultaneous induction of multiple stimulatory and inhibitory molecules. However, the overall impact of infected DC during T cell encounter results in suppression of T cell activation, indicating that inhibitory pathways functionally predominate. Inhibitory activity of infected DC is effected mainly by IL-10 and cyclooxygenase 2-mediated mechanisms, with soluble CD25 acting as an IL-2 scavenger as well as by the products of tryptophan catabolism. These inhibitory pathways are strictly TNF-dependent. In addition to direct infection, DC bearing this regulatory phenotype can be induced in vitro by a combination of signals including TNF, TLR2, and prostaglandin receptor ligation and by supernatants derived from the infected cells. Both infection-associated DC and other in vitro-induced regulatory DC are characterized by increased resistance to infection and enhanced bactericidal activity. Furthermore, myeloid DC expressing multiple regulatory molecules are identified in vivo in granuloma during listeriosis and tuberculosis. Based on the in vivo findings and the study of in vitro models, we propose that in granulomatous infections regulatory DC may possess dual function evolved to protect the host from disseminating infection via inhibition of granuloma destruction by T cells and control of pathogen spreading.
authors.affiliation: Genomics and Immunoregulation, Institute for Life and Medical Sciences, University of Bonn, Bonn, Germany.
authors.forename: Alexey
authors.initials: A
authors.lastname: Popov
authors.forename: Julia
authors.initials: J
authors.lastname: Driesen
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Abdullah
authors.forename: Claudia
authors.initials: C
authors.lastname: Wickenhauser
authors.forename: Marc
authors.initials: M
authors.lastname: Beyer
authors.forename: Svenja
authors.initials: S
authors.lastname: Debey-Pascher
authors.forename: Tomo
authors.initials: T
authors.lastname: Saric
authors.forename: Silke
authors.initials: S
authors.lastname: Kummer
authors.forename: Osamu
authors.initials: O
authors.lastname: Takikawa
authors.forename: Eugen
authors.initials: E
authors.lastname: Domann
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: D000276:Adjuvants, Immunologic / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology* / Q000382:microbiology*; D015536:Down-Regulation / Q000276:immunology*; D004790:Enzyme Induction / Q000276:immunology; D006099:Granuloma / Q000276:immunology / Q000382:microbiology; D006131:Growth Inhibitors / Q000096:biosynthesis / Q000502:physiology; D006801:Humans; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000378:metabolism; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000096:biosynthesis / Q000502:physiology; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology / Q000382:microbiology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D009000:Monocytes / Q000276:immunology / Q000382:microbiology; D022423:Myeloid Cells / Q000201:enzymology / Q000276:immunology* / Q000382:microbiology*; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000382:microbiology*
chemical_list: D000276:Adjuvants, Immunologic; D006131:Growth Inhibitors; D007166:Immunosuppressive Agents; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase