NLR Signaling Pathway

About NLR Pathway

The NLRs recognize various ligands from microbial pathogens, host cells, and environmental sources. Most NLRs act as a pattern recognition receptors (PRRs) to recognize the above ligands and activate the inflammatory response. However, some NLRs may not act as PRRs, but react to cytokines such as interferon. Activated NLRs has a variety of functions, which can be divided into four categories: inflammasome formation, signal transduction, transcriptional activation and autophagy. NOD2 removes pathogens by recruiting ATG16L1 to the plasma membrane of the bacterial entry site to induce autophagy. After NOD1 and NOD2 respectively recognize γ-D-glutamyl-meso-diaminopimelic acid (iE-DAP) and muramyl dipeptide (MDP), they activate NF-κB and MAPK signal pathways. NLRP2 and NLRP4 act as negative regulators of NF-κB pathway by modifying TRAF6. CIITA and NLRC5 are trans-activators of the major histocompatibility complex (MHC). NLRs, which form inflammasomes, convert cytokines into active IL-1 β and IL-18 by activating caspase-1. The NLR signaling pathway are responsible for detecting specific pathogen-associated molecules or host-derived damage signals in the cytosol and initiating the innate immune response.

References
1. Young Keun Kim, Jeon-Soo Shin, Moon H. Nahm (2016) NOD-Like Receptors in Infection, Immunity, and Diseases. Yonsei Med J. 57(1): 5–14.
2. TaiyuShen, XinweiLi, Juan J.Loor, YiweiZhu (2019) Hepatic nuclear factor kappa B signaling pathway and NLR family pyrin domain containing 3 inflammasome is over-activated in ketotic dairy. Journal of Dairy Science. Volume 102, Issue 11, Pages 10554-10563.
3. Mansi Saxena, Garabet Yeretssian (2014) NOD-like receptors: master regulators of inflammation and cancer. Front. Immunol. 5: 327.
4. Yi Wei Hu, Xiao Man Wu, Shi Si Ren, Lu Cao, Pin Nie & Ming Xian Chang (2017) NOD1 deficiency impairs CD44a/Lck as well as PI3K/Akt pathway. Scientific Reports volume 7, 2979.
5. Fernando J. Velloso, Marina Trombetta-Lima, Valesca Anschau, Mari C. Sogayar, Ricardo G. Correa (2019) NOD-like receptors: major players (and targets) in the interface between innate immunity and cancer. Biosci Rep. 39(4): BSR20181709.

For research use only. Not intended for any clinical use.