RNA sensors of the innate immune system and their detection of pathogens

Abstract

The innate immune system plays a critical role in pathogen recognition and initiation of protective immune response through the recognition of pathogen associated molecular patterns (PAMPs) by its pattern recognition receptors (PRRs). Nucleic acids including RNA and DNA have been recognized as very important PAMPs of pathogens especially for viruses. RNA are the major PAMPs of RNA viruses, to which most severe disease causing viruses belong thus posing a tougher challenge to human and animal health. Therefore, the understanding of the immune biology of RNA PRRs is critical for control of pathogen infections especially for RNA virus infections. RNA PRRs are comprised of TLR3, TLR7, TLR8, RIG-I, MDA5, NLRP3, NOD2, and some other minorities. This review introduces these RNA PRRs by describing the cellular localizations, ligand recognitions, activation mechanisms, cell signaling pathways, and recognition of pathogens; the cross-talks between various RNA PRRs are also reviewed. The deep insights of these RNA PRRs can be utilized to improve anti-viral immune response. © 2017 IUBMB Life, 69(5):297-304, 2017.

Post‐natal co‐development of the microbiota and gut barrier function follows different paths in the small and large intestine in piglets

“…However, whether fetal or neonatal intestinal epithelial stem cells displayed such predefined program or if additional signals in the neonatal intestinal environment, especially from the developing microbiota are needed to engage toward small intestine or colon epithelium was not clearly established. TLR3 binds double-strand RNA 32 and is implicated in virus sensing, among which rotavirus. Studies of infant meconium suggest that bacteria are present in the fetal gut prior to birth, meaning that colonization could occur prenatally.…”

“…Our data at PND0 would support the first hypothesis, that is, that small intestine and colonic cells are already programmed at birth for barrier and defense mechanisms. 32 The intestinal virome has been recently identified as a regulator of intestinal homeostasis and inflammation since the use of an antiviral cocktail or of TLR7 deficient mice results in severe chemically induced colitis. 27 Whether in utero bacteria influences divergent small intestine and colonic development deserves further investigations that were beyond the scope of the present study.…”

“…TLR7 and 8, whose expression increases with post-natal age, are receptors of single-strand RNA and thus act as potent RNA virus sensors. 32 The intestinal virome has been recently identified as a regulator of intestinal homeostasis and inflammation since the use of an antiviral cocktail or of TLR7 deficient mice results in severe chemically induced colitis. 33 Predominant viral groups F I G U R E 1 0 Correlation matrix of microbiota (at the family level) and mucosal parameters in the colon.…”

mRNA vaccines — a new era in vaccinology

“…1) (reviewed in REF. 35). Depending on the therapeutic application, this feature of mRNA could be beneficial or detrimental.…”

Retinoic acid‐inducible gene‐I, melanoma differentiation‐associated gene 5 and C‐X‐C motif chemokine ligand 10 are induced by a Toll‐like receptor 3 agonist in human brain microvascular endothelial cells

“…When microbes are invading from the bloodstream into the brain, the recognition of molecular patterns of microbes by pattern‐recognition receptors in BMEC is the initial step of innate immune reactions. Toll‐like receptor 3 (TLR3) is one of the pattern‐recognition receptors, and can recognize both viral double‐stranded RNA (dsRNA) and authentic dsRNA polyinosinic‐polycytidylic acid (poly IC) . Activation of TLR3 signaling triggers the upregulation of various molecules, such as cytokines and chemokines, which exert antiviral innate immune reactions.…”