Details

Autor(en) / Beteiligte

• Ku, Cheng-Lung
• von Bernuth, Horst
• Picard, Capucine
• Zhang, Shen-Ying
• Chang, Huey-Hsuan
• Yang, Kun
• Chrabieh, Maya
• Issekutz, Andrew C
• Cunningham, Coleen K
• Gallin, John
• Holland, Steven M
• Roifman, Chaim
• Ehl, Stephan
• Smart, Joanne
• Tang, Mimi
• Barrat, Franck J
• Levy, Ofer
• McDonald, Douglas
• Day-Good, Noorbibi K
• Miller, Richard
• Takada, Hidetoshi
• Hara, Toshiro
• Al-Hajjar, Sami
• Al-Ghonaium, Abdulaziz
• Speert, David
• Sanlaville, Damien
• Li, Xiaoxia
• Geissmann, Frédéric
• Vivier, Eric
• Maródi, László
• Garty, Ben-Zion
• Chapel, Helen
• Rodriguez-Gallego, Carlos
• Bossuyt, Xavier
• Abel, Laurent
• Puel, Anne
• Casanova, Jean-Laurent

Titel

Selective predisposition to bacterial infections in IRAK-4-deficient children: IRAK-4-dependent TLRs are otherwise redundant in protective immunity

Ist Teil von

• The Journal of experimental medicine, 2007-10, Vol.204 (10), p.2407-2422

Ort / Verlag

United States: Rockefeller University Press

Erscheinungsjahr

2007

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Human interleukin (IL) 1 receptor-associated kinase 4 (IRAK-4) deficiency is a recently discovered primary immunodeficiency that impairs Toll/IL-1R immunity, except for the Toll-like receptor (TLR) 3- and TLR4-interferon (IFN)-alpha/beta pathways. The clinical and immunological phenotype remains largely unknown. We diagnosed up to 28 patients with IRAK-4 deficiency, tested blood TLR responses for individual leukocyte subsets, and TLR responses for multiple cytokines. The patients' peripheral blood mononuclear cells (PBMCs) did not induce the 11 non-IFN cytokines tested upon activation with TLR agonists other than the nonspecific TLR3 agonist poly(I:C). The patients' individual cell subsets from both myeloid (granulocytes, monocytes, monocyte-derived dendritic cells [MDDCs], myeloid DCs [MDCs], and plasmacytoid DCs) and lymphoid (B, T, and NK cells) lineages did not respond to the TLR agonists that stimulated control cells, with the exception of residual responses to poly(I:C) and lipopolysaccharide in MDCs and MDDCs. Most patients (22 out of 28; 79%) suffered from invasive pneumococcal disease, which was often recurrent (13 out of 22; 59%). Other infections were rare, with the exception of severe staphylococcal disease (9 out of 28; 32%). Almost half of the patients died (12 out of 28; 43%). No death and no invasive infection occurred in patients older than 8 and 14 yr, respectively. The IRAK-4-dependent TLRs and IL-1Rs are therefore vital for childhood immunity to pyogenic bacteria, particularly Streptococcus pneumoniae. Conversely, IRAK-4-dependent human TLRs appear to play a redundant role in protective immunity to most infections, at most limited to childhood immunity to some pyogenic bacteria.