Editors' ChoiceImmunology

Revealing Flaws in Immune Defenses

STKE  01 Apr 2003:
Vol. 2003, Issue 176, pp. tw132-TW132
DOI: 10.1126/stke.2003.176.tw132

In response to innate inflammatory signals, Toll-like receptors, and interleukin-1 (IL-1) receptors activate the NF-κb and p38 mitogen-activated protein kinase (MAPK) pathways by recruiting the IL-1 receptor-associated kinase (IRAK) to their intracellular Toll-IL-1 receptor domains. IRAK-4 deficiency in mice leads to a profound immune deficiency to a range of bacterial and viral infections. Picard et al. describe three patients with inherited mutations in the IRAK-4 gene that lead to impaired immunity to certain common species of pyogenic bacterial. However, unlike the situation in mice, human IRAK-4 appears to be redundant in coping with other types of viral, bacterial, and fungal infection.

C. Picard, A. Puel, M. Bonnet, C.-L. Ku, J. Bustamante, K. Yang, C. Soudais, S. Dupuis, J. Feinberg, C. Fieschi, C. Elbim, R. Hitchcock, D. Lammas, G. Davies, A. Al-Ghonaium, H. Al-Rayes, S. Al-Jumaah, S. Al-Hajjar, I. Z. Al-Mohsen, H. H. Frayha, R. Rucker, T. R. Hawn, A. Aderem, H. Tufenkeji, S. Haraguchi, N. K. Day, R. A. Good, M.-A. Gougerot-Pocidalo, A. Ozinsky, J.-L. Casanova, Pyogenic bacterial infections in humans with IRAK-4 deficiency. Science 299, 2076-2079 (2003). [Abstract] [Full Text]