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Review
. 2013 Dec 25:4:468.
doi: 10.3389/fimmu.2013.00468.

Sensing microbial RNA in the cytosol

Affiliations
Review

Sensing microbial RNA in the cytosol

Nicolas Vabret et al. Front Immunol. .

Abstract

The innate immune system faces the difficult task of keeping a fine balance between sensitive detection of microbial presence and avoidance of autoimmunity. To this aim, key mechanisms of innate responses rely on isolation of pathogens in specialized subcellular compartments, or sensing of specific microbial patterns absent from the host. Efficient detection of foreign RNA in the cytosol requires an additional layer of complexity from the immune system. In this particular case, innate sensors should be able to distinguish self and non-self molecules that share several similar properties. In this review, we discuss this interplay between cytosolic pattern recognition receptors and the microbial RNA they detect. We describe how microbial RNAs gain access to the cytosol, which receptors they activate and counter-strategies developed by microorganisms to avoid this response.

Keywords: DExD/H-box helicases; RIG-I-like receptors; RNA helicases; cytosol; innate immune escape; pathogen-associated molecular patterns; pattern recognition receptors.

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Figures

Figure 1
Figure 1
Cytosolic recognition of microbial RNA. Genomic RNA from RNA viruses access the cytosol immediately after the cell entry step of the replication cycle, where it may be amplified by viral RNA-dependent RNA polymerase (RdRp). Genomic DNA from DNA viruses is transcribed by viral or cellular RNA polymerase, including the cytosolic RNA polymerase III. Bacterial RNA can access the cytosol through the activity of auxiliary secretion systems or during passive leakage of phagosomal products. Once in the cytosol, microbial RNA binds different families of PRRs classified as RLRs, non-RLR helicases, and other receptors. Downstream signaling pathways include activation of MAVS, TRIF, and the NLRP3 inflammasome. Black arrows, RNA entry; red arrows, signaling pathways.

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