NOD‐like receptors interfacing the immune and reproductive systems

Abstract

Nucleotide-binding oligomerization domain receptors (NOD-like receptors, NLRs) are intracellular proteins that are chiefly known for their critical functions in inflammatory responses and host defense against microbial pathogens. Several NLRs have been demonstrated to assemble inflammasomes or to engage transcriptional signaling cascades that result in the production of pro-inflammatory cytokines and bactericidal factors. In recent years, NLRs have also emerged as key regulators of early mammalian embryogenesis and reproduction. A subset of phylogenetically related NLRs represents a new class of maternal effect genes that are highly expressed in maturing oocytes and pre-implantation embryos. Mutations in several of these NLRs have been linked to hereditary reproductive defects and imprinting diseases. In this review, we discuss the expression profiles, the emerging functions and molecular mode of action of these NLRs with newly recognized roles at the interfaces of the immune and reproductive systems. In addition, we provide an overview of coding mutations in NLRs that have been associated with human reproductive diseases, and outline crucial outstanding questions in this emerging research field

The NLR family pyrin domain–containing 11 protein contributes to the regulation of inflammatory signaling

“…SNPs in NLRP11 were associated with age at natural menopause (10,11). NLRP11 might thus have reproductionrelated functions such as have been reported for the NLRP proteins NLRP2, NLRP5 and NLRP7 (7,12). As well, a single nucleotide polymorphism (SNP), located in the NLRP11 gene was associated with susceptibility to Crohn's Disease, an inflammatory bowel disease (13) and a duplication encompassing the NLRP11 gene was identified in patients with juvenile idiopathic arthritis, a rare inflammatory disease in children (14), suggesting further functionalities of NLRP11 in the regulation of inflammatory pathways in humans.…”

Familial Mediterranean fever mutations lift the obligatory requirement for microtubules in Pyrin inflammasome activation

“…FMF | Pyrin | inflammasome | colchicine | microtubules I nflammasomes are multiprotein complexes that culminate in processing of caspase-1, thereby promoting maturation of proIL-1β and proIL-18 into their active forms (1). Several inflammasome platforms have been described, and the concerted actions of inflammasomes frequently are of utmost importance for effective protection of the host against harmful environmental agents and infections (1).…”

“…Several inflammasome platforms have been described, and the concerted actions of inflammasomes frequently are of utmost importance for effective protection of the host against harmful environmental agents and infections (1). Conversely, mutations in genes coding for inflammasome components and regulators cause debilitating systemic autoinflammatory diseases, of which cryopyrin-associated periodic syndromes (CAPS; NLRP3 mutations), autoinflammation with infantile enterocolitis (AIFEC; NLRC4 mutations), hyperimmunoglobulinemia syndrome (HIDS; MVK mutations) and familial Mediterranean fever (FMF; MEFV mutations) are notable examples (2,3).…”

NOD1 and NOD2 control the invasiveness of trophoblast cells via the MAPK/p38 signaling pathway in human first-trimester pregnancy

“…Perhaps these are self-protection mechanisms in the human body. When invasive bacteria have escaped from membrane PRRs, the cytoplasm defending barrier can response to them immediately [26], and, at the same time, the signals can lead to amplification.…”