Editing Peptidoglycan (section)

==== NOD-like receptors ====
Probably the most well-known receptors of peptidoglycan are the [[NOD-like receptor]]s (NLRs), mainly [[NOD1]] and [[NOD2]]. The NOD1 receptor is activated after iE-DAP (γ-d-glutamyl-meso-diaminopimelic acid) binding, while NOD2 recognizes MDP (muramyl dipeptide), by their [[LRR domain]]s.<ref name="Sun-2022" /> Activation leads to self-oligomerization, resulting in activation of two signalling cascades. One triggers activation of [[NF-κB]] (through RIP2, [[MAP3K7|TAK1]] and [[IκB kinase|IKK]]<ref name="Murphy-2017">{{Cite book | vauthors = Murphy K, Weaver C, Janeway C |title=Janeway's immunobiology |year=2017 |isbn=978-0-8153-4505-3 |edition=9th |location=New York |publisher=Garland Science |pages=45, 96–98 |oclc=933586700}}</ref>), second leads to [[Mitogen-activated protein kinase|MAPK]] signalling cascade. Activation of these pathways induces production of inflammatory [[cytokine]]s and [[chemokine]]s.<ref name="Wolf-2018" />

NOD1 is expressed by diverse cell types, including myeloid phagocytes, epithelial cells<ref name="Wolf-2018" /> and neurons.<ref name="Gonzalez-Santana-2020" /> NOD2 is expressed in monocytes and macrophages, epithelial intestinal cells, [[Paneth cell]]s, [[dendritic cell]]s, [[osteoblast]]s, keratinocytes and other epithelial cell types.<ref name="Bastos-2021" /> As [[cytosol]]ic sensors, NOD1 and NOD2 must either detect bacteria that enter the cytosol, or peptidoglycan must be degraded to generate fragments that must be transported into the cytosol for these sensors to function.<ref name="Wolf-2018" />

Recently, it was demonstrated that [[NLRP3]] is activated by peptidoglycan, through a mechanism that is independent of NOD1 and NOD2.<ref name="Bastos-2021" /> In macrophages, N-acetylglucosamine generated by peptidoglycan degradation was found to inhibit hexokinase activity and induce its release from the [[Mitochondrion|mitochondrial]] [[membrane]]. It promotes NLRP3 [[inflammasome]] activation through a mechanism triggered by increased mitochondrial membrane permeability.<ref name="Bastos-2021" />

[[NLRP1]] is also considered as a cytoplasmic sensor of peptidoglycan. It can sense MDP and promote [[Interleukin-1 family|IL-1]] secretion through binding NOD2.<ref name="Sun-2022" /><ref name="Bersch-2021" />