Abstract
Since they were first described as cytosolic sensors of microbial molecules a decade ago, the Nod-like receptors (NLRs) have been shown to have many different and important roles in various aspects of immune and inflammatory responses, ranging from antimicrobial mechanisms to control of adaptive responses. In this review, we focus on the interplay between NLRs and autophagy, an evolutionarily conserved mechanism that is crucial for homeostasis and has recently been shown to be involved in the protective response against infections. Furthermore, the association between mutations of NLRs as well as proteins that form the autophagic machinery and inflammatory diseases such as Crohn’s disease highlight the importance of these proteins and their interactions in the regulation of inflammation.
Highlights
Homeostasis in multicellular organisms is dependent on the ability to detect and adapt to a myriad of environmental variations and insults, including exposure to microbes
This detection is based on the recognition of “microbial-associated molecular patterns” (MAMPs), which represent a signature of microbial origin, such as lipopolysaccharide (LPS), peptidoglycan (PG), flagellin, and nucleic acids from bacteria and viruses, or of “danger-associated molecular patterns” (DAMPs), which indicate the existence of cellular damage, such as extracellular ATP and HGMB1 by “pattern recognition molecules”(PRMs)
While we demonstrated that the adaptor protein Rip2 and NF-κB activation is dispensable for autophagy induction because Rip2-deficient fibroblasts displayed similar numbers of S. flexneri targeted to autophagosomes, Cooney et al found that Rip2-deficient dendritic cells (DCs) had reduced levels of autophagy
Summary
Reviewed by: Ashley Mansell, Monash Institute of Medical Research, Australia Cheol-Heui Yun, Seoul National University, South Korea. Since they were first described as cytosolic sensors of microbial molecules a decade ago, the Nod-like receptors (NLRs) have been shown to have many different and important roles in various aspects of immune and inflammatory responses, ranging from antimicrobial mechanisms to control of adaptive responses. We focus on the interplay between NLRs and autophagy, an evolutionarily conserved mechanism that is crucial for homeostasis and has recently been shown to be involved in the protective response against infections.
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