| First Author | Wurm R | Year | 2015 |
| Journal | Eur J Immunol | Volume | 45 |
| Issue | 5 | Pages | 1366-76 |
| PubMed ID | 25675948 | Mgi Jnum | J:229783 |
| Mgi Id | MGI:5754457 | Doi | 10.1002/eji.201445116 |
| Citation | Wurm R, et al. (2015) Protective dendritic cell responses against listeriosis induced by the short form of the deubiquitinating enzyme CYLD are inhibited by full-length CYLD. Eur J Immunol 45(5):1366-76 |
| abstractText | 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-kappaB 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 CD8alpha(+) DCs, which are crucial for the establishment of listeriosis in the spleen, was not affected. However, NF-kappaB 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-gamma-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-gamma 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. |
