Dendritic Cells Coordinate Innate Immunity via MyD88 Signaling to Control Listeria monocytogenes Infection

• Published in: Cell reports (Cambridge) 2014-02, Vol.6 (4), p.698-708
• Main Authors: Arnold-Schrauf, Catharina, Dudek, Markus, Dielmann, Anastasia, Pace, Luigia, Swallow, Maxine, Kruse, Friederike, Kühl, Anja A., Holzmann, Bernhard, Berod, Luciana, Sparwasser, Tim
• Format: Article
• Language: English
• Subjects: Animals; CD11c Antigen - genetics; CD11c Antigen - metabolism; CD8 Antigens - genetics; CD8 Antigens - metabolism; Cytokines - genetics; Cytokines - metabolism; Dendritic Cells - immunology; Dendritic Cells - metabolism; Immunity, Innate; Listeria monocytogenes; Listeriosis - immunology; Listeriosis - metabolism; Mice; Myeloid Differentiation Factor 88 - genetics; Myeloid Differentiation Factor 88 - metabolism; Neutrophils - immunology; Signal Transduction; T-Lymphocytes - immunology
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2014.01.023

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. [Display omitted] •Dendritic cell (DC) MyD88 signaling triggers the innate immune response•CD8a+ cDC infection and bacterial dissemination are controlled by MyD88 signaling•Intrinsic MyD88 signaling is not required for inflammatory monocyte activation Innate immune activation via the MyD88 signaling pathway is a key event during many infections. However, whether cell-type-specific signaling in dendritic cells (DCs) is sufficient for infection control is unknown. Here, Sparwasser and colleagues demonstrate that MyD88 signaling in DCs critically coordinates innate immune activation and thereby prevents bacterial dissemination during infection with Listeria monocytogenes, whereas its function in other myeloid cells, such as inflammatory monocytes, is dispensable. These findings suggest that MyD88-dependent DC activation initiates bacterial infection control.