title: TLR2 mediates phagocytosis and autophagy through JNK signaling pathway in Staphylococcus aureus-stimulated RAW264.7 cells.
abstract: Toll-like receptor 2 (TLR2) is involved in phagocytosis and autophagy to enhance host innate immune response to bacterial infection. TLR2 has been reported to participate in the recognition of Staphylococcus aureus (S. aureus). However, the role of TLR2 in phagocytosis and autophagy in S. aureus-stimulated macrophages and the underlying mechanisms as yet remain unclear. In the present study, stimulation of mouse macrophage cell line RAW264.7 with S. aureus activated multiple signaling pathways including mitogen-activated protein kinases (MAPKs), myeloid differentiation factor 88 (MyD88), phosphatidylinositide 3-kinase (PI3K) and Rac1 and triggered autophagy process. Knockdown of TLR2 by siRNA significantly reduced phagocytosis and autophagy of macrophages upon S. aureus infection. Interestingly, TLR2 siRNA markedly attenuated S. aureus-induced phosphorylation of c-Jun N-terminal kinase (JNK) but not p38 or extracellular regulated protein kinase (ERK) in macrophages. Similarly, SP600125, a JNK inhibitor, also down-regulated phagocytosis and autophagy in S. aureus-stimulated macrophages. Furthermore, TLR2 siRNA and SP600125 simultaneous treatment showed similar phagocytosis and autophagy compared to that in TLR2 siRNA treatment alone. Collectively, our results indicate that TLR2 may be critical for phagocytosis and autophagy through JNK signaling pathway, and provide an underlying mechanistic link between innate immune receptor and induction of phagocytosis and autophagy in S. aureus-stimulated macrophages.
authors.affiliation: Department of Pulmonary, Anhui Geriatric Institute, The First Affiliated Hospital of Anhui Medical University, Jixi Road 218, Hefei, Anhui 230022, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Fang
authors.affiliation: Department of Pulmonary, Anhui Geriatric Institute, The First Affiliated Hospital of Anhui Medical University, Jixi Road 218, Hefei, Anhui 230022, PR China.
authors.forename: Hui-Mei
authors.initials: HM
authors.lastname: Wu
authors.affiliation: Department of Pulmonary, Anhui Geriatric Institute, The First Affiliated Hospital of Anhui Medical University, Jixi Road 218, Hefei, Anhui 230022, PR China.
authors.forename: Pei-Shan
authors.initials: PS
authors.lastname: Ding
authors.affiliation: Department of Pulmonary, Anhui Geriatric Institute, The First Affiliated Hospital of Anhui Medical University, Jixi Road 218, Hefei, Anhui 230022, PR China. Electronic address: rongyuliu@gmail.com.
authors.forename: Rong-Yu
authors.initials: RY
authors.lastname: Liu
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D010766:Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D013211:Staphylococcus aureus / Q000472:pathogenicity*; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000873:Anthracenes; D053594:Myeloid Differentiation Factor 88; D034741:RNA, Small Interfering; D051195:Toll-Like Receptor 2; C432165:pyrazolanthrone; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Autophagy; Macrophages; Phagocytosis; Staphylococcus aureus; Toll-like receptor 2; c-Jun N-terminal kinase