the quorum sensing volatile molecule 2-amino acetophenon modulates host immune responses in a manner that promotes life with unwanted guests群体感应挥发性分子2-amino acetophenon调节宿主免疫反应的方式促进生活不受欢迎的客人.pdfVIP

The Quorum Sensing Volatile Molecule 2-Amino Acetophenon Modulates Host Immune Responses in a Manner that Promotes Life with Unwanted Guests Arunava Bandyopadhaya1,2,3., Meenu Kesarwani1,2,3.¤, Yok-Ai Que1,2,3, Jianxin He1,2,3, Katie Padfield1,3, Ronald Tompkins1,3, Laurence G. Rahme1,2,3* 1 Department of Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, United States of America, 2 Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, United States of America, 3 Shriners Hospitals for Children Boston, Boston, Massachusetts, United States of America Abstract Increasing evidence indicates that bacterial quorum sensing (QS) signals are important mediators of immunomodulation. However, whether microbes utilize these immunomodulatory signals to maintain infection remain unclear. Here, we show that the Pseudomonas aeruginosa QS-regulated molecule 2-amino acetophenone (2-AA) modulates host immune responses in a manner that increases host ability to cope with this pathogen. Mice treated with 2-AA prior to infection had a 90% survival compared to 10% survival rate observed in the non-pretreated infected mice. Whilst 2-AA stimulation activates key innate immune response pathways involving mitogen-activated protein kinases (MAPKs), nuclear factor (NF)-kB, and pro- inflammatory cytokines, it attenuates immune response activation upon pretreatment, most likely by upregulating anti- inflammatory cytokines. 2-AA host pretreatment is characterized by a transcriptionally regulated block of c-JUN N-terminal kinase (JNK) and NF-kB activation, with relatively preserved activation of extracellular regulated kinase (ERK) 1/2. These kinase changes lead to CCAAT/enhancer-binding protein-b (c/EBPb) activation and format