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The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.

Syk kinase signalling couples to the Nlrp3 inflammasome for anti-fungal host defence

Gross, Olaf, Poeck, Hendrik, Bscheider, Michael, Dostert, Catherine, Hannesschläger, Nicole, Endres, Stefan, Hartmann, Gunther, Tardivel, Aubry, Schweighoffer, Edina, Tybulewicz, Victor, Mocsai, Attila, Tschopp, Jürg, Ruland, Jürgen·2009·Nature
DOI 10.1038/nature07965
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Abstract

Fungal infections represent a serious threat, particularly in immunocompromised patients. Interleukin-1beta (IL-1beta) is a key pro-inflammatory factor in innate antifungal immunity. The mechanism by which the mammalian immune system regulates IL-1beta production after fungal recognition is unclear. Two signals are generally required for IL-1beta production: an NF-kappaB-dependent signal that induces the synthesis of pro-IL-1beta (p35), and a second signal that triggers proteolytic pro-IL-1beta processing to produce bioactive IL-1beta (p17) via Caspase-1-containing multiprotein complexes called inflammasomes. Here we demonstrate that the tyrosine kinase Syk, operating downstream of several immunoreceptor tyrosine-based activation motif (ITAM)-coupled fungal pattern recognition receptors, controls both pro-IL-1beta synthesis and inflammasome activation after cell stimulation with Candida albicans. Whereas Syk signalling for pro-IL-1beta synthesis selectively uses the Card9 pathway, inflammasome activation by the fungus involves reactive oxygen species production and potassium efflux. Genetic deletion or pharmalogical inhibition of Syk selectively abrogated inflammasome activation by C. albicans but not by inflammasome activators such as Salmonella typhimurium or the bacterial toxin nigericin. Nlrp3 (also known as NALP3) was identified as the critical NOD-like receptor family member that transduces the fungal recognition signal to the inflammasome adaptor Asc (Pycard) for Caspa…

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Crossref · 10.1038/nature07965

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Citations

Cites

Research works printed but not linked: 21

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  2. Vonk, A. G. et al. Endogenous interleukin (IL)-1α and IL-1β are crucial for host defense against disseminated candidiasis. J. Infect. Dis. 193, 1419–1426 (2006) · DOI
  3. Yu, H. B. & Finlay, B. B. The caspase-1 inflammasome: a pilot of innate immune responses. Cell Host Microbe 4, 198–208 (2008) · DOI
  4. Bugarcic, A. et al. Human and mouse macrophage-inducible C-type lectin (Mincle) bind Candida albicans . Glycobiology 18, 679–685 (2008) · DOI
  5. Yamasaki, S. et al. Mincle is an ITAM-coupled activating receptor that senses damaged cells. Nature Immunol. 9, 1179–1188 (2008) · DOI · Paper page
  6. Gross, O. et al. Card9 controls a non-TLR signalling pathway for innate anti-fungal immunity. Nature 442, 651–656 (2006) · DOI
  7. Hara, H. et al. The adaptor protein CARD9 is essential for the activation of myeloid cells through ITAM-associated and Toll-like receptors. Nature Immunol. 8, 619–629 (2007) · DOI
  8. Braselmann, S. et al. R406, an orally available spleen tyrosine kinase inhibitor blocks Fc receptor signaling and reduces immune complex-mediated inflammation. J. Pharmacol. Exp. Ther. 319, 998–1008 (2006) · DOI
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  16. Boyden, E. D. & Dietrich, W. F. Nalp1b controls mouse macrophage susceptibility to anthrax lethal toxin. Nature Genet. 38, 240–244 (2006) · DOI
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  19. Weinblatt, M. E. et al. Treatment of rheumatoid arthritis with a Syk kinase inhibitor: a twelve-week, randomized, placebo-controlled trial. Arthritis Rheum. 58, 3309–3318 (2008) · DOI
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Metadata

Authors
Gross, O., Poeck, H., Bscheider, M., Dostert, C., Hannesschläger, N., Endres, S., Hartmann, G., Tardivel, A., Schweighoffer, E., Tybulewicz, V., Mocsai, A., Tschopp, J., & Ruland, J.
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2009-04-01
Volume
459
Issue
7245
Pages
433-436
ISSN
  • 0028-0836
  • 1476-4687
DOI
10.1038/nature07965
Cited by
819
References
8
Language
en
Licence
www.springer.com/tdm (tdm)

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