Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

Science 327 (5963): 286-290

Copyright © 2010 by the American Association for the Advancement of Science

How the Noninflammasome NLRs Function in the Innate Immune System

Jenny P. Y. Ting,1,2,3,* Joseph A. Duncan,4,5 Yu Lei2,3

Abstract: NLR (nucleotide-binding domain, leucine-rich repeat–containing) proteins have rapidly emerged as central regulators of immunity and inflammation with demonstrated relevance to human diseases. Much attention has focused on the ability of several NLRs to activate the inflammasome complex and drive proteolytic processing of inflammatory cytokines; however, NLRs also regulate important inflammasome-independent functions in the immune system. We discuss several of these functions, including the regulation of canonical and noncanonical NF-{kappa}B activation, mitogen-activated protein kinase activation, cytokine and chemokine production, antimicrobial reactive oxygen species production, type I interferon production, and ribonuclease L activity. We also explore the mechanistic basis of these functions and describe current challenges in the field.

1 Department of Microbiology-Immunology, University of North Carolina, Chapel Hill, NC 27599, USA.
2 Curriculum of Oral Biology, University of North Carolina, Chapel Hill, NC 27599, USA.
3 Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
4 Department of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
5 Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599, USA.

* To whom correspondence should be addressed. E-mail: jpyting{at}med.unc.edu


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The Characterization of Sponge NLRs Provides Insight into the Origin and Evolution of This Innate Immune Gene Family in Animals.
B. Yuen, J. M. Bayes, and S. M. Degnan (2014)
Mol. Biol. Evol. 31, 106-120
   Abstract »    Full Text »    PDF »
Novel Role of NOD2 in Mediating Ca2+ Signaling: Evidence From NOD2-Regulated Podocyte TRPC6 Channels in Hyperhomocysteinemia.
H. Han, Y. Wang, X. Li, P.-A. Wang, X. Wei, W. Liang, G. Ding, X. Yu, C. Bao, Y. Zhang, et al. (2013)
Hypertension 62, 506-511
   Abstract »    Full Text »    PDF »
Antimicrobial peptide elicitors: New hope for the post-antibiotic era.
E. P. M. de Oca (2013)
Innate Immunity 19, 227-241
   Abstract »    Full Text »    PDF »
Impact of Host Membrane Pore Formation by the Yersinia pseudotuberculosis Type III Secretion System on the Macrophage Innate Immune Response.
L. Kwuan, W. Adams, and V. Auerbuch (2013)
Infect. Immun. 81, 905-914
   Abstract »    Full Text »    PDF »
Multiple Binding Sites on the Pyrin Domain of ASC Protein Allow Self-association and Interaction with NLRP3 Protein.
P. R. Vajjhala, R. E. Mirams, and J. M. Hill (2012)
J. Biol. Chem. 287, 41732-41743
   Abstract »    Full Text »    PDF »
Regulation of Class I Major Histocompatibility Complex (MHC) by Nucleotide-binding Domain, Leucine-rich Repeat-containing (NLR) Proteins.
G. R. Robbins, A. D. Truax, B. K. Davis, L. Zhang, W. J. Brickey, and J. P.- Y. Ting (2012)
J. Biol. Chem. 287, 24294-24303
   Abstract »    Full Text »    PDF »
Crohn's Disease Risk Alleles on the NOD2 Locus Have Been Maintained by Natural Selection on Standing Variation.
S. Nakagome, S. Mano, L. Kozlowski, J. M. Bujnicki, H. Shibata, Y. Fukumaki, J. R. Kidd, K. K. Kidd, S. Kawamura, and H. Oota (2012)
Mol. Biol. Evol. 29, 1569-1585
   Abstract »    Full Text »    PDF »
Metabolism, Pharmacokinetics, Tissue Distribution, and Stability Studies of the Prodrug Analog of an Anti-Hepatitis B Virus Dinucleoside Phosphorothioate.
J. E. Coughlin, R. K. Pandey, S. Padmanabhan, K. G. O'Loughlin, J. Marquis, C. E. Green, J. C. Mirsalis, and R. P. Iyer (2012)
Drug Metab. Dispos. 40, 970-981
   Abstract »    Full Text »    PDF »
NLRC5 Deficiency Selectively Impairs MHC Class I- Dependent Lymphocyte Killing by Cytotoxic T Cells.
F. Staehli, K. Ludigs, L. X. Heinz, Q. Seguin-Estevez, I. Ferrero, M. Braun, K. Schroder, M. Rebsamen, A. Tardivel, C. Mattmann, et al. (2012)
J. Immunol. 188, 3820-3828
   Abstract »    Full Text »    PDF »
Staphylococcus aureus {alpha}-Hemolysin Mediates Virulence in a Murine Model of Severe Pneumonia Through Activation of the NLRP3 Inflammasome.
C. Kebaier, R. R. Chamberland, I. C. Allen, X. Gao, P. M. Broglie, J. D. Hall, C. Jania, C. M. Doerschuk, S. L. Tilley, and J. A. Duncan (2012)
The Journal of Infectious Disease 205, 807-817
   Abstract »    Full Text »    PDF »
The Fire Within: Cardiac Inflammatory Signaling in Health and Disease.
M. Coggins and A. Rosenzweig (2012)
Circ. Res. 110, 116-125
   Abstract »    Full Text »    PDF »
Nod1 Activation by Bacterial iE-DAP Induces Maternal-Fetal Inflammation and Preterm Labor.
I. Cardenas, M. J. Mulla, K. Myrtolli, A. K. Sfakianaki, E. R. Norwitz, S. Tadesse, S. Guller, and V. M. Abrahams (2011)
J. Immunol. 187, 980-986
   Abstract »    Full Text »    PDF »
Transient Receptor Potential Melastatin 2 (TRPM2) ion channel is required for innate immunity against Listeria monocytogenes.
H. Knowles, J. W. Heizer, Y. Li, K. Chapman, C. A. Ogden, K. Andreasen, E. Shapland, G. Kucera, J. Mogan, J. Humann, et al. (2011)
PNAS 108, 11578-11583
   Abstract »    Full Text »    PDF »
The Evolution and Regulation of the Mucosal Immune Complexity in the Basal Chordate Amphioxus.
S. Huang, X. Wang, Q. Yan, L. Guo, S. Yuan, G. Huang, H. Huang, J. Li, M. Dong, S. Chen, et al. (2011)
J. Immunol. 186, 2042-2055
   Abstract »    Full Text »    PDF »
Mitochondrial Membrane Potential Is Required for MAVS-Mediated Antiviral Signaling.
T. Koshiba, K. Yasukawa, Y. Yanagi, and S.-i. Kawabata (2011)
Science Signaling 4, ra7
   Abstract »    Full Text »    PDF »
Cutting Edge: NLRC5-Dependent Activation of the Inflammasome.
B. K. Davis, R. A. Roberts, M. T. Huang, S. B. Willingham, B. J. Conti, W. J. Brickey, B. R. Barker, M. Kwan, D. J. Taxman, M.-A. Accavitti-Loper, et al. (2011)
J. Immunol. 186, 1333-1337
   Abstract »    Full Text »    PDF »
NLRC5 Deficiency Does Not Influence Cytokine Induction by Virus and Bacteria Infections.
H. Kumar, S. Pandey, J. Zou, Y. Kumagai, K. Takahashi, S. Akira, and T. Kawai (2011)
J. Immunol. 186, 994-1000
   Abstract »    Full Text »    PDF »
The Airway Epithelium: Soldier in the Fight against Respiratory Viruses.
M. Vareille, E. Kieninger, M. R. Edwards, and N. Regamey (2011)
Clin. Microbiol. Rev. 24, 210-229
   Abstract »    Full Text »    PDF »
Modification of Cysteine 179 of I{kappa}B{alpha} Kinase by Nimbolide Leads to Down-regulation of NF-{kappa}B-regulated Cell Survival and Proliferative Proteins and Sensitization of Tumor Cells to Chemotherapeutic Agents.
S. C. Gupta, S. Prasad, S. Reuter, R. Kannappan, V. R. Yadav, J. Ravindran, P. S. Hema, M. M. Chaturvedi, M. Nair, and B. B. Aggarwal (2010)
J. Biol. Chem. 285, 35406-35417
   Abstract »    Full Text »    PDF »
RNase L releases a small RNA from HCV RNA that refolds into a potent PAMP.
K. Malathi, T. Saito, N. Crochet, D. J. Barton, M. Gale Jr, and R. H. Silverman (2010)
RNA 16, 2108-2119
   Abstract »    Full Text »    PDF »
Cutting Edge: NLRP12 Controls Dendritic and Myeloid Cell Migration To Affect Contact Hypersensitivity.
J. C. Arthur, J. D. Lich, Z. Ye, I. C. Allen, D. Gris, J. E. Wilson, M. Schneider, K. E. Roney, B. P. O'Connor, C. B. Moore, et al. (2010)
J. Immunol. 185, 4515-4519
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882