type i interferon production induced by streptococcus pyogenes-derived nucleic acids is required for host protection链球菌引起的i型干扰素生产pyogenes-derived核酸主机需要保护.pdfVIP

Type I Interferon Production Induced by Streptococcus pyogenes-Derived Nucleic Acids Is Required for Host Protection 1 1 2 1 1 2 Nina Gratz , Harald Hartweger , Ulrich Matt , Franz Kratochvill , Marton Janos , Stefanie Sigel , Barbara 3 4 2 1 Drobits , Xiao-Dong Li , Sylvia Knapp , Pavel Kovarik * 1 Max F. Perutz Laboratories, Department of Microbiology, Immunobiology and Genetics, University of Vienna, Vienna, Austria, 2 CEMM, Research Center for Molecular Medicine of the Austrian Academy of Sciences and Department of Internal Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna, Austria, 3 Institute for Cancer Research, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria, 4 Department of Molecular Biology, UT Southwestern Medical Center, Dallas, Texas, United States of America Abstract Streptococcus pyogenes is a Gram-positive human pathogen that is recognized by yet unknown pattern recognition receptors (PRRs). Engagement of these receptor molecules during infection with S. pyogenes, a largely extracellular bacterium with limited capacity for intracellular survival, causes innate immune cells to produce inflammatory mediators such as TNF, but also type I interferon (IFN). Here we show that signaling elicited by type I IFNs is required for successful defense of mice against lethal subcutaneous cellulitis caused by S. pyogenes. Type I IFN signaling was accompanied with reduced neutrophil recruitment to the site of infection. Mechanistic analysis revealed that macrophages and conventional dendritic cells (cDCs) employ different