title: Protective dendritic cell responses against listeriosis induced by the short form of the deubiquitinating enzyme CYLD are inhibited by full-length CYLD.
abstract: The deubiquitinating enzyme CYLD is an important tumor suppressor and inhibitor of immune responses. In contrast to full-length CYLD, the immunological function of the naturally occurring short splice variant of CYLD (sCYLD) is insufficiently described. Previously, we showed that DCs, which lack full-length CYLD but express sCYLD, exhibit augmented NF-κB and DC activation. To explore the function of sCYLD in infection, we investigated whether DC-specific sCYLD regulates the pathogenesis of listeriosis. Upon Listeria monocytogenes infection of CD11c-Cre Cyld(ex7/8 fl/fl) mice, infection of CD8α(+) DCs, which are crucial for the establishment of listeriosis in the spleen, was not affected. However, NF-κB activity of CD11c-Cre Cyld(ex7/8 fl/fl) DCs was increased, while activation of ERK and p38 was normal. In addition, CD11c-Cre Cyld(ex7/8 fl/fl) DCs produced more TNF, IL-10, and IL-12 upon infection, which led to enhanced stimulation of IFN-γ-producing NK cells. In addition CD11c-Cre Cyld(ex7/8 fl/fl) DCs presented Listeria Ag more efficiently to CD8(+) T cells resulting in a stronger pathogen-specific CD8(+) T-cell proliferation and more IFN-γ production. Collectively, the improved innate and adaptive immunity and survival during listeriosis identify the DC-specific FL-CYLD/sCYLD balance as a potential target to modulate NK-cell and Ag-specific CD8(+) T-cell responses.
authors: Institute of Medical Microbiology and Hospital Hygiene, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
authors: Rebecca
authors: R
authors: Wurm
authors: Institute of Medical Microbiology and Hospital Hygiene, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
authors: Sissy
authors: S
authors: Just
authors: Institute of Medical Microbiology and Hospital Hygiene, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
authors: Xu
authors: X
authors: Wang
authors: Institute of Medical Microbiology and Hospital Hygiene, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
authors: Katharina
authors: K
authors: Wex
authors: Institute of Medical Microbiology and Hospital Hygiene, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
authors: Ursula
authors: U
authors: Schmid
authors: Center for Pathophysiology of Toulouse-Purpan, INSERM U1043, Toulouse, France.
authors: Nicolas
authors: N
authors: Blanchard
authors: Institute of Molecular Medicine, University of Mainz, Mainz, Germany.
authors: Ari
authors: A
authors: Waisman
authors: Institute of Immunology, University of Mainz, Mainz, Germany.
authors: Hans-Jörg
authors: HJ
authors: Schild
authors: Department of Neuropathology, University Hospital Cologne, Cologne, Germany.
authors: Martina
authors: M
authors: Deckert
authors: Institute of Experimental Internal Medicine, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
authors: Michael
authors: M
authors: Naumann
authors: Institute of Medical Microbiology and Hospital Hygiene, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.|Organ-Specific Immune Regulation, Helmholtz Institute for Infection Research, Braunschweig, Germany.
authors: Dirk
authors: D
authors: Schlüter
authors: Institute of Medical Microbiology and Hospital Hygiene, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.|Organ-Specific Immune Regulation, Helmholtz Institute for Infection Research, Braunschweig, Germany.
authors: Gopala
authors: G
authors: Nishanth
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D039521:CD11c Antigen / Q000235:genetics / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D000074749:Deubiquitinating Enzyme CYLD; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D007962:Leukocytes / Q000276:immunology / Q000473:pathology; D008089:Listeria monocytogenes / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity; D008088:Listeriosis / Q000201:enzymology* / Q000276:immunology* / Q000382:microbiology; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D013154:Spleen / Q000276:immunology / Q000473:pathology; D015854:Up-Regulation
chemical_list: D039521:CD11c Antigen; D016827:CD8 Antigens; C431698:CD8alpha antigen; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D007527:Isoenzymes; D016328:NF-kappa B; C511601:CYLD protein, mouse; D000074749:Deubiquitinating Enzyme CYLD; D003546:Cysteine Endopeptidases
keywords: CYLD; Dendritic cell; Infection; Listeria