Nod-like Receptors: Critical Intracellular Sensors for Host Protection and Cell Death in Microbial and Parasitic Infections

Abstract

Cell death is an essential immunological apparatus of host defense, but dysregulation of mutually inclusive cell deaths poses severe threats during microbial and parasitic infections leading to deleterious consequences in the pathological progression of infectious diseases. Nucleotide-binding oligomerization domain (NOD)-Leucine-rich repeats (LRR)-containing receptors (NLRs), also called nucleotide-binding oligomerization (NOD)-like receptors (NLRs), are major cytosolic pattern recognition receptors (PRRs), their involvement in the orchestration of innate immunity and host defense against bacteria, viruses, fungi and parasites, often results in the cleavage of gasdermin and the release of IL-1β and IL-18, should be tightly regulated. NLRs are functionally diverse and tissue-specific PRRs expressed by both immune and non-immune cells. Beyond the inflammasome activation, NLRs are also involved in NF-κB and MAPK activation signaling, the regulation of type I IFN (IFN-I) production and the inflammatory cell death during microbial infections. Recent advancements of NLRs biology revealed its possible interplay with pyroptotic cell death and inflammatory mediators, such as caspase 1, caspase 11, IFN-I and GSDMD. This review provides the most updated information that caspase 8 skews the NLRP3 inflammasome activation in PANoptosis during pathogen infection. We also update multidimensional roles of NLRP12 in regulating innate immunity in a content-dependent manner: novel interference of NLRP12 on TLRs and NOD derived-signaling cascade, and the recently unveiled regulatory property of NLRP12 in production of type I IFN. Future prospects of exploring NLRs in controlling cell death during parasitic and microbial infection were highlighted.

The Emerging Role of RNA Modifications in the Regulation of Antiviral Innate Immunity

“…Different PRRs must distinguish the non-self molecules from the self through chemical patterns. To date, several kinds of PRRs, including TLRs, RLRs, cyclic GMP-AMP synthase (cGAS; Schoggins et al, 2014;Aguirre et al, 2017;Ma et al, 2021;Yu et al, 2021), C-type lectin receptors (CLRs), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), and AIM2-like receptors (ALRs), have been utilized by host cells in recognition of viral PAMPs (Akira et al, 2006;Crowl et al, 2017;Babamale and Chen, 2021;Chou et al, 2021;de Oliveira Mann and Hornung, 2021). As the most important component in virus particles, viral-derived RNAs/DNAs are released into the host cell cytoplasm at the early stage of infection.…”

Gut Microbiome in Inflammatory Bowel Disease: Role in Pathogenesis, Dietary Modulation, and Colitis-Associated Colon Cancer

“…The host defense systems are subsequently activated through the innate immune system, such as antimicrobial peptides (AMPs), which are stimulated by microbiota metabolites [ 79 ]. Defensins are the most common AMP in the gut and are effective in controlling targeted bacteria by forming pores in their membrane [ 80 ]. Concurrently, epithelial cells and immune cells of the intestinal wall recognize these bacteria through pattern-recognition receptors (PRRs).…”

Revisiting Regulated Cell Death Responses in Viral Infections

“…The NLRP3 is the most widely studied and characterized NLR inflammasome, activated during viral infection with highly diverse viruses [64,110,111]. The NLRP3 inflammasome is thought to respond to a change in cellular homeostasis and ionic balance rather than a specific microbial or viral ligand [112,113]. Over and above established microbial settings, NLRP3 contributes to immunopathology and innate and adaptive immunity quality during viral infection [114].…”