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Pyogenic Bacterial Infections in Humans with IRAK-4 Deficiency
Abstract
Members of the Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) superfamily share an intracytoplasmic Toll–IL-1 receptor (TIR) domain, which mediates recruitment of the interleukin-1 receptor–associated kinase (IRAK) complex via TIR-containing adapter molecules. We describe three unrelated children with inherited IRAK-4 deficiency. Their blood and fibroblast cells did not activate nuclear factor κB and mitogen-activated protein kinase (MAPK) and failed to induce downstream cytokines in response to any of the known ligands of TIR-bearing receptors. The otherwise healthy children developed infections caused by pyogenic bacteria. These findings suggest that, in humans, the TIR-IRAK signaling pathway is crucial for protective immunity against specific bacteria but is redundant against most other microorganisms.
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Cited by
Akira, S., & Takeda, K. (2004) · Nature reviews. Immunology · doi:10.1038/nri1391 · Cited by 8,312
Toll-like receptors and their crosstalk with other innate receptors in infection and immunity
Kawai, T., & Akira, S. (2011) · Immunity · doi:10.1016/j.immuni.2011.05.006 · Cited by 3,658
LPS/TLR4 signal transduction pathway
Lu, Y.-C., Yeh, W.-C., & Ohashi, P. S. (2008) · Cytokine · doi:10.1016/j.cyto.2008.01.006 · Cited by 3,301
Helical Assembly in the MyD88-IRAK4-IRAK2 Complex in TLR/IL-1R Signalling
Lin, S.-C., Lo, Y.-C., & Wu, H. (2010) · Nature · doi:10.1038/nature09121 · Cited by 1,111
TLR3 Deficiency in Patients with Herpes Simplex Encephalitis
Zhang, S.-Y., Jouanguy, E., Ugolini, S., Smahi, A., Elain, G., Romero, P., Segal, D., Sancho-Shimizu, V., Lorenzo, L., Puel, A., et al. (2007) · Science · doi:10.1126/science.1139522 · Cited by 1,057
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Metadata
- Authors
- Picard, C., Puel, A., Bonnet, M., Ku, C.-L., Bustamante, J., Yang, K., Soudais, C., Dupuis, S., Feinberg, J., Fieschi, C., Elbim, C., Hitchcock, R., Lammas, D., Davies, G., Al-Ghonaium, A., Al-Rayes, H., Al-Jumaah, S., Al-Hajjar, S., Al-Mohsen, I. Z., Frayha, H. H., Rucker, R., Hawn, T. R., Aderem, A., Tufenkeji, H., Haraguchi, S., Day, N. K., Good, R. A., Gougerot-Pocidalo, M.-A., Ozinsky, A., & Casanova, J.-L.
- Venue
- Science
- Published
- 2003-03-28
- Volume
- 299
- Issue
- 5615
- Pages
- 2076-2079
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W4241949506
- Cited by
- 826
- References
- 0
- FWCI
- 19.13
- Type
- journal article
- Language
- en
- Open access
- closed
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- The paper
- Picard, C., Puel, A., Bonnet, M., Ku, C.-L., Bustamante, J., Yang, K., Soudais, C., Dupuis, S., Feinberg, J., Fieschi, C., Elbim, C., Hitchcock, R., Lammas, D., Davies, G., Al-Ghonaium, A., Al-Rayes, H., Al-Jumaah, S., Al-Hajjar, S., Al-Mohsen, I. Z., . . . Casanova, J.-L. (2003). Pyogenic Bacterial Infections in Humans with IRAK-4 Deficiency. Science. https://doi.org/10.1126/science.1081902
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