Dendritic cells coordinate innate immunity via MyD88 signaling to control Listeria monocytogenes infection.

Cell reports

PubMedID: 24529704

Arnold-Schrauf C, Dudek M, Dielmann A, Pace L, Swallow M, Kruse F, Kühl AA, Holzmann B, Berod L, Sparwasser T. Dendritic cells coordinate innate immunity via MyD88 signaling to control Listeria monocytogenes infection. Cell Rep. 2014;6(4):698-708.
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 CD8a(+) 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.