title: Nocardia farcinica activates human dendritic cells and induces secretion of interleukin-23 (IL-23) rather than IL-12p70.
abstract: Studying the interaction of dendritic cells (DCs) with bacteria controlled by T-cell-mediated immune responses may reveal novel adjuvants for the induction of cellular immunity. Murine studies and the observation that nocardias infect predominantly immunosuppressed patients have suggested that these bacteria may possess an adjuvant potential. Moreover, adjuvants on the basis of the nocardial cell wall have been applied in clinical studies. Since the handling of adjuvants by DCs may determine the type of immune responses induced by a vaccine, the present study aimed at investigating the interaction of immature human monocyte-derived DCs with live or inactivated Nocardia farcinica in vitro and determining the cellular phenotypic changes as well as alterations in characteristic functions, such as phagocytosis, induction of T-cell proliferation, and cytokine secretion. Human DCs ingested N. farcinica and eradicated the bacterium intracellularly. DCs exposed to inactivated N. farcinica were activated, i.e., they developed a mature phenotype, downregulated their phagocytic capacity, and stimulated allogeneic T cells in mixed leukocyte reactions. Soluble factors were not involved in this process. To elucidate the potential adjuvant effect of N. farcinica on the induction of T-cell-mediated immune responses, we characterized the cytokines produced by nocardia-exposed DCs and detected substantial amounts of tumor necrosis factor alpha (TNF-α) and interleukin-12 p40 (IL-12p40). However, nocardia-treated DCs secreted only small amounts of IL-12p70, which were significantly smaller than the amounts of IL-23. Thus, N. farcinica activates DCs, but adjuvants based on this bacterium may have only a limited capacity to induce Th1 immune responses.
authors.affiliation: Institute of Microbiology and Hygiene, Department of Infection Immunology, Charité-University Medicine Berlin, Berlin, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Eisenblätter
authors.forename: Ariane
authors.initials: A
authors.lastname: Buchal
authors.forename: Hermine
authors.initials: H
authors.lastname: Gayum
authors.forename: Edith
authors.initials: E
authors.lastname: Jasny
authors.forename: Pablo
authors.initials: P
authors.lastname: Renner Viveros
authors.forename: Timo
authors.initials: T
authors.lastname: Ulrichs
authors.forename: Thomas
authors.initials: T
authors.lastname: Schneider
authors.forename: Ralf R
authors.initials: RR
authors.lastname: Schumann
authors.forename: Janine
authors.initials: J
authors.lastname: Zweigner
authors.forename: Ralf
authors.initials: R
authors.lastname: Ignatius
mesh_terms: D000276:Adjuvants, Immunologic; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis*; D053762:Interleukin-12 Subunit p40 / Q000276:immunology; D053759:Interleukin-23 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D009615:Nocardia / Q000145:classification / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D053762:Interleukin-12 Subunit p40; D053759:Interleukin-23; D018664:Interleukin-12