NOD-like receptors

NOD-like receptors (NLRs) are a group of pattern recognition receptors that are expressed in the cell cytosol. They can sense molecules that are associated with infection (for example, bacterial peptidoglycans) and induce inflammatory immune responses that help clear the infection.

Latest Research and Reviews

  • Research |

    Dendritic cells (DCs) have been suggested to express a functional NLRP3 inflammasome. Gerlic and colleagues demonstrate, however, that bone marrow–derived DCs completely lack NLRP3 inflammasome activity and that the bulk of splenic DCs lack or have only minimal activity.

    • Ziv Erlich
    • , Inbar Shlomovitz
    • , Liat Edry-Botzer
    • , Hadar Cohen
    • , Daniel Frank
    • , Hanqing Wang
    • , Andrew M. Lew
    • , Kate E. Lawlor
    • , Yifan Zhan
    • , James E. Vince
    •  & Motti Gerlic
  • Research | | open

    Guo et al. identify the role of acidic glycosphingolipids as the mechanism of action of the pore-forming protein complex βγ-CAT from the frog. This study suggests that βγ-CAT binds to both gangliosides and sulfatides, initiating its endocytosis and ultimately exerting its antimicrobial effects.

    • Xiao-Long Guo
    • , Ling-Zhen Liu
    • , Qi-Quan Wang
    • , Jin-Yang Liang
    • , Wen-Hui Lee
    • , Yang Xiang
    • , Sheng-An Li
    •  & Yun Zhang
  • Research | | open

    Mutations in nucleotide-binding oligomerization domain protein 12 (NLRP12) are known to effect inflammatory processes. Here the authors show that NLRP12-mediated proteasomal degradation of NOD2 in monocytes promotes bacterial tolerance and colonisation in a model of enteric infection.

    • Sylvain Normand
    • , Nadine Waldschmitt
    • , Andreas Neerincx
    • , Ruben Julio Martinez-Torres
    • , Camille Chauvin
    • , Aurélie Couturier-Maillard
    • , Olivier Boulard
    • , Laetitia Cobret
    • , Fawaz Awad
    • , Ludovic Huot
    • , Andre Ribeiro-Ribeiro
    • , Katja Lautz
    • , Richard Ruez
    • , Myriam Delacre
    • , Clovis Bondu
    • , Martin Guilliams
    • , Charlotte Scott
    • , Anthony Segal
    • , Serge Amselem
    • , David Hot
    • , Sonia Karabina
    • , Erwin Bohn
    • , Bernhard Ryffel
    • , Lionel F. Poulin
    • , Thomas A. Kufer
    •  & Mathias Chamaillard
  • Research | | open

    The innate immune receptor NOD2 is tightly regulated to ensure beneficial antimicrobial immunity. Here the authors show that the H2A deubiquitinase MYSM1 restrains NOD2 signaling by removing lysine 63 (K63), K27, M1 but not K48 polyubiquitin chains from its downstream adaptor protein RIP2.

    • Swarupa Panda
    •  & Nelson O. Gekara
  • Research | | open

    Binding of bacterial peptidoglycan muramyl dipeptides induces NOD2 activation and signalling via the downstream adaptor kinase RIP2. Here the authors show that RIP2 forms filaments via its CARD domain, analyse the structure of the CARD filaments and demonstrate the requirement of RIP2 polymerisation for the activation of NF-κB by NOD2.

    • Erika Pellegrini
    • , Ambroise Desfosses
    • , Arndt Wallmann
    • , Wiebke Manuela Schulze
    • , Kristina Rehbein
    • , Philippe Mas
    • , Luca Signor
    • , Stephanie Gaudon
    • , Grasilda Zenkeviciute
    • , Michael Hons
    • , Helene Malet
    • , Irina Gutsche
    • , Carsten Sachse
    • , Guy Schoehn
    • , Hartmut Oschkinat
    •  & Stephen Cusack
  • Research | | open

    The inflammasome is normally activated by pathogens to induce tissue inflammation. Here the authors show that, in mouse experimental colitis models, Nlrp1 inflammasome sensor activates IL-18 to reduce beneficial colonic Clostridiales species, thereby decreasing microbial butyrate and its protective effects on colitis.

    • Hazel Tye
    • , Chien-Hsiung Yu
    • , Lisa A. Simms
    • , Marcel R. de Zoete
    • , Man Lyang Kim
    • , Martha Zakrzewski
    • , Jocelyn S. Penington
    • , Cassandra R. Harapas
    • , Fernando Souza-Fonseca-Guimaraes
    • , Leesa F. Wockner
    • , Adele Preaudet
    • , Lisa A. Mielke
    • , Stephen A. Wilcox
    • , Yasunori Ogura
    • , Sinead C. Corr
    • , Komal Kanojia
    • , Konstantinos A. Kouremenos
    • , David P. De Souza
    • , Malcolm J. McConville
    • , Richard A. Flavell
    • , Motti Gerlic
    • , Benjamin T. Kile
    • , Anthony T. Papenfuss
    • , Tracy L. Putoczki
    • , Graham L. Radford-Smith
    •  & Seth L. Masters

News and Comment

  • News and Views |

    New findings show that the NLRP3 inflammasome is inactivated by disassembly of the inflammasome mediated by the kinase PKA and that this regulation might be negated in NLRP3-gain-of-function diseases.

    • Karen V Swanson
    •  & Jenny P-Y Ting
    Nature Immunology 17, 1137-1138
  • Correspondence |

    • Lieselotte Vande Walle
    • , Daniel Jiménez Fernández
    • , Dieter Demon
    • , Naomi Van Laethem
    • , Filip Van Hauwermeiren
    • , Hanne Van Gorp
    • , Nina Van Opdenbosch
    • , Nobuhiko Kayagaki
    •  & Mohamed Lamkanfi
    Nature 534, E1-E4
  • News and Views |

    The NLRP3 inflammasome has broad biomedical relevance, but its activation mechanisms are incompletely understood. NEK7, a kinase that regulates microtubules during mitosis, is identified as a critical and selective upstream regulator of NLRP3 inflammasome activation.

    • Filip Van Hauwermeiren
    •  & Mohamed Lamkanfi
    Nature Immunology 17, 223-224
  • News and Views |

    Paneth cell dysfunction has been linked to Crohn's disease. Nod2 and LRRK2, two genetic susceptibility factors for this disease, are now shown to have a role in regulating the sorting of lysozyme in Paneth cells and its secretion into the crypt space and, ultimately, in maintenance of the intestinal barrier.

    • Juliana D B Rocha
    • , Michael G Schlossmacher
    •  & Dana J Philpott
    Nature Immunology 16, 898-900