@article{300e530e4edc4996added3ce9b28edc5,
title = "NLRC4 inflammasomes in dendritic cells regulate noncognate effector function by memory CD8 + T cells",
abstract = "Memory T cells exert antigen-independent effector functions, but how these responses are regulated is unclear. We discovered an in vivo link between flagellin-induced NLRC4 inflammasome activation in splenic dendritic cells (DCs) and host protective interferon-γ (IFN-γ) secretion by noncognate memory CD8 + T cells, which could be activated by Salmonella enterica serovar Typhimurium, Yersinia pseudotuberculosis and Pseudomonas aeruginosa. We show that CD8α + DCs were particularly efficient at sensing bacterial flagellin through NLRC4 inflammasomes. Although this activation released interleukin 18 (IL-18) and IL-1β, only IL-18 was required for IFN-γ production by memory CD8 + T cells. Conversely, only the release of IL-1β, but not IL-18, depended on priming signals mediated by Toll-like receptors. These findings provide a comprehensive mechanistic framework for the regulation of noncognate memory T cell responses during bacterial immunity.",
author = "Andreas Kupz and Greta Guarda and Thomas Gebhardt and Sander, {Leif E.} and Short, {Kirsty R.} and Diavatopoulos, {Dimitri A.} and Wijburg, {Odilia L C} and Hanwei Cao and Waithman, {Jason C.} and Weisan Chen and Daniel Fernandez-Ruiz and Whitney, {Paul G.} and Heath, {William R.} and Roy Curtiss and J{\"u}rg Tschopp and Strugnell, {Richard A.} and Sammy Bedoui",
note = "Funding Information: We thank D. Maskell (University of Cambridge) for mutant S. Typhimurium strain SL1344 ΔmsbB; R. Robins-Browne (University of Melbourne) for motile E. coli MG1655 and Y. pseudotuberculosis B14; C. Whitchurch (University of Technology, Sydney) for Pseudomonas aeruginosa and P. aeruginosa PAKMS591 (fliC − P. aeruginosa); A. Walduck (University of Melbourne) for Helicobacter pylori SS1; F.R. Carbone, E.L. Hartland, A.M. Lew, L. Alexopoulou, S. Akira, R.A. Flavell, D.I. Godfrey and A.G. Brooks for reagents, bacteria, mice and discussions; and A. Turner for assistance. Supported by the National Health and Medical Research Council of Australia (Career Development Awards to T.G., O.L.C.W. and S.B.), the Louis-Jeantet Foundation (G.G. and J.T.) and the Gates Foundation, through the Grand Challenges in Health program (R.C., O.L.C.W. and R.A.S.).",
year = "2012",
month = feb,
doi = "10.1038/ni.2195",
language = "English (US)",
volume = "13",
pages = "162--169",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "2",
}