Conventional Dendritic Cells Confer Protection against Mouse Cytomegalovirus Infection via TLR9 and MyD88 Signaling
Franz Puttur,
Marcela Francozo,
Gülhas Solmaz,
Carlos Bueno,
Marc Lindenberg,
Melanie Gohmert,
Maxine Swallow,
Dejene Tufa,
Roland Jacobs,
Stefan Lienenklaus,
Anja A. Kühl,
Lisa Borkner,
Luka Cicin-Sain,
Bernard Holzmann,
Hermann Wagner,
Luciana Berod,
Tim Sparwasser
Affiliations
Franz Puttur
Institute of Infection Immunology, Centre for Experimental and Clinical Infection Research (Twincore), Hannover Medical School (MHH) and Helmholtz Centre for Infection Research (HZI), 30625 Hannover, Germany
Marcela Francozo
Institute of Infection Immunology, Centre for Experimental and Clinical Infection Research (Twincore), Hannover Medical School (MHH) and Helmholtz Centre for Infection Research (HZI), 30625 Hannover, Germany
Gülhas Solmaz
Institute of Infection Immunology, Centre for Experimental and Clinical Infection Research (Twincore), Hannover Medical School (MHH) and Helmholtz Centre for Infection Research (HZI), 30625 Hannover, Germany
Carlos Bueno
Institute of Infection Immunology, Centre for Experimental and Clinical Infection Research (Twincore), Hannover Medical School (MHH) and Helmholtz Centre for Infection Research (HZI), 30625 Hannover, Germany
Marc Lindenberg
Institute of Infection Immunology, Centre for Experimental and Clinical Infection Research (Twincore), Hannover Medical School (MHH) and Helmholtz Centre for Infection Research (HZI), 30625 Hannover, Germany
Melanie Gohmert
Institute of Infection Immunology, Centre for Experimental and Clinical Infection Research (Twincore), Hannover Medical School (MHH) and Helmholtz Centre for Infection Research (HZI), 30625 Hannover, Germany
Maxine Swallow
Institute of Infection Immunology, Centre for Experimental and Clinical Infection Research (Twincore), Hannover Medical School (MHH) and Helmholtz Centre for Infection Research (HZI), 30625 Hannover, Germany
Dejene Tufa
Department of Clinical Immunology and Rheumatology, MHH, 30625 Hannover, Germany
Roland Jacobs
Department of Clinical Immunology and Rheumatology, MHH, 30625 Hannover, Germany
Stefan Lienenklaus
Institute for Laboratory Animal Science, MHH, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany
Anja A. Kühl
Medical Department (Gastroenterology, Infectious Diseases and Rheumatology)/Research Center ImmunoScience, Charité–Universitätsmedizin Berlin, Campus Benjamin Franklin, 12200 Berlin, Germany
Lisa Borkner
Department for Vaccinology/Immune Aging and Chronic Infection, HZI, 38124 Braunschweig, Germany
Luka Cicin-Sain
Department for Vaccinology/Immune Aging and Chronic Infection, HZI, 38124 Braunschweig, Germany
Bernard Holzmann
Department of Surgery, Technische Universität München, 81675 Munich, Germany
Hermann Wagner
Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, 81675 Munich, Germany
Luciana Berod
Institute of Infection Immunology, Centre for Experimental and Clinical Infection Research (Twincore), Hannover Medical School (MHH) and Helmholtz Centre for Infection Research (HZI), 30625 Hannover, Germany
Tim Sparwasser
Institute of Infection Immunology, Centre for Experimental and Clinical Infection Research (Twincore), Hannover Medical School (MHH) and Helmholtz Centre for Infection Research (HZI), 30625 Hannover, Germany
Cytomegalovirus (CMV) is an opportunistic virus severely infecting immunocompromised individuals. In mice, endosomal Toll-like receptor 9 (TLR9) and downstream myeloid differentiation factor 88 (MyD88) are central to activating innate immune responses against mouse CMV (MCMV). In this respect, the cell-specific contribution of these pathways in initiating anti-MCMV immunity remains unclear. Using transgenic mice, we demonstrate that TLR9/MyD88 signaling selectively in CD11c+ dendritic cells (DCs) strongly enhances MCMV clearance by boosting natural killer (NK) cell CD69 expression and IFN-γ production. In addition, we show that in the absence of plasmacytoid DCs (pDCs), conventional DCs (cDCs) promote robust NK cell effector function and MCMV clearance in a TLR9/MyD88-dependent manner. Simultaneously, cDC-derived IL-15 regulates NK cell degranulation by TLR9/MyD88-independent mechanisms. Overall, we compartmentalize the cellular contribution of TLR9 and MyD88 signaling in individual DC subsets and evaluate the mechanism by which cDCs control MCMV immunity.
