期刊
MBIO
卷 5, 期 2, 页码 -出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/mBio.01006-14
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资金
- NIAID Mucosal Immunity Study Team (MIST) program [U01AI095611]
- NIH [5T32AI007647-13, 1K99AI095320-01]
- NIH-National Cancer Institute (NCI) shared resources grant [5R24 CA095823-04]
- National Science Foundation (NSF) Major Research Instrumentation grant [DBI-9724504]
- NIH shared instrumentation grant [1 S10 RR0 9145-01]
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 In phagocytic cells, RIG-I is obsolete for detection of Salmonella infection.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.
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