Dendritic Cells Coordinate Innate Immunity via MyD88 Signaling to Control Listeria monocytogenes Infection
Catharina Arnold-Schrauf,
Markus Dudek,
Anastasia Dielmann,
Luigia Pace,
Maxine Swallow,
Friederike Kruse,
Anja A. Kühl,
Bernhard Holzmann,
Luciana Berod,
Tim Sparwasser
Affiliations
Catharina Arnold-Schrauf
Institute for Infection Immunology, TWINCORE, Center for Experimental and Clinical Infection Research, a Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Center for Infection Research (HZI), 30625 Hannover, Germany
Markus Dudek
Institute for Infection Immunology, TWINCORE, Center for Experimental and Clinical Infection Research, a Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Center for Infection Research (HZI), 30625 Hannover, Germany
Anastasia Dielmann
Institute for Infection Immunology, TWINCORE, Center for Experimental and Clinical Infection Research, a Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Center for Infection Research (HZI), 30625 Hannover, Germany
Luigia Pace
Institut National de la Santé et de la Recherche Médicale (INSERM) U932, Institut Curie, 75005 Paris, France
Maxine Swallow
Institute for Infection Immunology, TWINCORE, Center for Experimental and Clinical Infection Research, a Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Center for Infection Research (HZI), 30625 Hannover, Germany
Friederike Kruse
Institute for Infection Immunology, TWINCORE, Center for Experimental and Clinical Infection Research, a Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Center for Infection Research (HZI), 30625 Hannover, Germany
Anja A. Kühl
Department of Medicine I for Gastroenterology, Infectious Disease and Rheumatology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, 12203 Berlin, Germany
Bernhard Holzmann
Chirurgische Klinik und Poliklinik, Technische Universität München, 81675 Munich, Germany
Luciana Berod
Institute for Infection Immunology, TWINCORE, Center for Experimental and Clinical Infection Research, a Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Center for Infection Research (HZI), 30625 Hannover, Germany
Tim Sparwasser
Institute for Infection Immunology, TWINCORE, Center for Experimental and Clinical Infection Research, a Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Center for Infection Research (HZI), 30625 Hannover, Germany
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 T cell 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 in vivo.
