TY - JOUR
T1 - Dendritic Cells Coordinate Innate Immunity via MyD88 Signaling to Control Listeria monocytogenes Infection
AU - Arnold-Schrauf, Catharina
AU - Dudek, Markus
AU - Dielmann, Anastasia
AU - Pace, Luigia
AU - Swallow, Maxine
AU - Kruse, Friederike
AU - Kühl, Anja A.
AU - Holzmann, Bernhard
AU - Berod, Luciana
AU - Sparwasser, Tim
N1 - Funding Information:
We thank S. Dippel, E. Ermeling, and C. Jänke for expert technical support. We also thank H.W. Mittrücker, P. Dresing, and S. Scheu for initial support with the Listeria infection model and J. Hühn, S. Halle, S. Cording, and S. Amigorena for helpful discussions. Finally, we acknowledge the assistance of the Cell Sorting Core Facility of the Hannover Medical School, supported in part by Braukmann-Wittenberg-Herz-Stiftung and the Deutsche Forschungsgemeinschaft (DFG). C.A.S. received a PhD stipend as well as personal support from the Boehringer Ingelheim Fonds, Foundation for Basic Research in Medicine. M.D. received a PhD stipend from the DFG in the framework of the International Research Training Group (IRTG) 1273. This project was financed by SFB900.
PY - 2014
Y1 - 2014
N2 - Listeria monocytogenes (LM), a facultative intracellular Gram-positive pathogen, can cause life-threatening infections in humans. In mice, the signaling cascade downstream of the myeloid differentiation factor 88 (MyD88) is essential for proper innate immune activation against LM, as MyD88-deficient mice succumb early to infection. Here, we show that MyD88 signaling in dendritic cells (DCs) is sufficient to mediate the protective innate response, including the production of proinflammatory cytokines, neutrophil infiltration, bacterial clearance, and full protection from lethal infection. We also demonstrate that MyD88 signaling by DCs controls the infection rates of CD8α+ cDCs and thus limits the spread of LM to the Tcell areas. Furthermore, in mice expressing MyD88 in DCs, inflammatory monocytes, which are required for bacterial clearance, are activated independently of intrinsic MyD88 signaling. In conclusion, CD11c+ conventional DCs critically integrate pathogen-derived signals via MyD88 signaling during early infection with LM invivo.
AB - Listeria monocytogenes (LM), a facultative intracellular Gram-positive pathogen, can cause life-threatening infections in humans. In mice, the signaling cascade downstream of the myeloid differentiation factor 88 (MyD88) is essential for proper innate immune activation against LM, as MyD88-deficient mice succumb early to infection. Here, we show that MyD88 signaling in dendritic cells (DCs) is sufficient to mediate the protective innate response, including the production of proinflammatory cytokines, neutrophil infiltration, bacterial clearance, and full protection from lethal infection. We also demonstrate that MyD88 signaling by DCs controls the infection rates of CD8α+ cDCs and thus limits the spread of LM to the Tcell areas. Furthermore, in mice expressing MyD88 in DCs, inflammatory monocytes, which are required for bacterial clearance, are activated independently of intrinsic MyD88 signaling. In conclusion, CD11c+ conventional DCs critically integrate pathogen-derived signals via MyD88 signaling during early infection with LM invivo.
UR - https://www.scopus.com/pages/publications/84896697606
U2 - 10.1016/j.celrep.2014.01.023
DO - 10.1016/j.celrep.2014.01.023
M3 - Article
C2 - 24529704
AN - SCOPUS:84896697606
SN - 2639-1856
VL - 6
SP - 698
EP - 708
JO - Cell Reports
JF - Cell Reports
IS - 4
ER -