title: RIG-I detects mRNA of intracellular Salmonella enterica serovar Typhimurium during bacterial infection.
abstract: The cytoplasmic helicase RIG-I is an established sensor for viral 5'-triphosphorylated RNA species. Recently, RIG-I was also implicated in the detection of intracellular bacteria. However, little is known about the host cell specificity of this process and the bacterial pathogen-associated molecular pattern (PAMP) that activates RIG-I. Here we show that RNA of Salmonella enterica serovar Typhimurium activates production of beta interferon in a RIG-I-dependent fashion only in nonphagocytic cells. In phagocytic cells, RIG-I is obsolete for detection of Salmonella infection. We further demonstrate that Salmonella mRNA reaches the cytoplasm during infection and is thus accessible for RIG-I. The results from next-generation sequencing analysis of RIG-I-associated RNA suggest that coding bacterial mRNAs represent the activating PAMP. IMPORTANCE S. Typhimurium is a major food-borne pathogen. After fecal-oral transmission, it can infect epithelial cells in the gut as well as immune cells (mainly macrophages, dendritic cells, and M cells). The innate host immune system relies on a growing number of sensors that detect pathogen-associated molecular patterns (PAMPs) to launch a first broad-spectrum response to invading pathogens. Successful detection of a given pathogen depends on colocalization of host sensors and PAMPs as well as potential countermeasures of the pathogen during infection. RIG-I-like helicases were mainly associated with detection of RNA viruses. Our work shows that S. Typhimurium is detected by RIG-I during infection specifically in nonimmune cells.
authors.forename: Mirco
authors.initials: M
authors.lastname: Schmolke
authors.forename: Jenish R
authors.initials: JR
authors.lastname: Patel
authors.forename: Elisa
authors.initials: E
authors.lastname: de Castro
authors.forename: Maria T
authors.initials: MT
authors.lastname: Sánchez-Aparicio
authors.forename: Melissa B
authors.initials: MB
authors.lastname: Uccellini
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Miller
authors.forename: Balaji
authors.initials: B
authors.lastname: Manicassamy
authors.forename: Takashi
authors.initials: T
authors.lastname: Satoh
authors.forename: Taro
authors.initials: T
authors.lastname: Kawai
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Miriam
authors.initials: M
authors.lastname: Merad
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
mesh_terms: D000818:Animals; D002460:Cell Line; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000276:immunology* / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D016899:Interferon-beta / Q000276:immunology / Q000378:metabolism; D051379:Mice; D011485:Protein Binding; D012329:RNA, Bacterial / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000276:immunology* / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology* / Q000378:metabolism; D012486:Salmonella typhimurium / Q000276:immunology*
chemical_list: D012329:RNA, Bacterial; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D016899:Interferon-beta; C503356:Ddx58 protein, mouse; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases