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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Selective predisposition to bacterial infections in IRAK-4-deficient children: IRAK-4-dependent TLRs are otherwise redundant in protective immunity
Journal of Experimental Medicine, Volume 204, No. 10, Year 2007
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Description
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)-α/β 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. JEM © The Rockefeller University Press.
Authors & Co-Authors
Ku, Cheng-Lung
France, Paris
L'institut Des Maladies Génétiques Imagine
France, Paris
Université Paris Cité
von Bernuth, Horst
France, Paris
L'institut Des Maladies Génétiques Imagine
France, Paris
Université Paris Cité
Germany, Dresden
Technische Universität Dresden
Pïcard, Capucine
France, Paris
L'institut Des Maladies Génétiques Imagine
France, Paris
Université Paris Cité
France, Paris
Hôpital Necker Enfants Malades
Zhang, Shenying
France, Paris
L'institut Des Maladies Génétiques Imagine
France, Paris
Université Paris Cité
Chang, Huey Hsuan
France, Paris
L'institut Des Maladies Génétiques Imagine
France, Paris
Université Paris Cité
Yang, Kun
France, Paris
L'institut Des Maladies Génétiques Imagine
France, Paris
Université Paris Cité
Chrabieh, Maya
France, Paris
L'institut Des Maladies Génétiques Imagine
France, Paris
Université Paris Cité
Issekutz, Andrew C.
Canada, Halifax
Dalhousie University
Cunningham, Coleen K.
United States, Durham
Duke University Medical Center
Gallin, John I.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Holland, Steven M.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Roifman, Chaim M.
Canada, Toronto
Hospital for Sick Children University of Toronto
Ehl, Stephan R.
Germany, Freiburg Im Breisgau
Universität Freiburg
Smart, Joanne M.
Australia, Melbourne
Royal Children's Hospital, Melbourne
Tang, Mimi L.K.
Australia, Melbourne
Royal Children's Hospital, Melbourne
Barrat, Franck J.
United States, Berkeley
Dynavax Technologies Corporation
Levy, Ofer
United States, Boston
Boston Children's Hospital
United States, Boston
Harvard Medical School
McDonald, Douglas R.
United States, Boston
Boston Children's Hospital
United States, Boston
Harvard Medical School
Day, Noorbibi K.B.
United States, St Petersburg
University of South Florida St. Petersburg
Miller, Richard L.
United States, Saint Paul
3m Usa
Takada, Hidetoshi
Japan, Fukuoka
Graduate School of Medical Sciences
Hara, Toshirou
Japan, Fukuoka
Graduate School of Medical Sciences
Al-Hajjar, Sami Hussain
Saudi Arabia, Riyadh
King Faisal Specialist Hospital and Research Centre
Al-Ghonaium, Abdulaziz
Saudi Arabia, Riyadh
King Faisal Specialist Hospital and Research Centre
Speert, David Paul
Canada, Vancouver
Bc Children's Hospital Research Institute
Sanlaville, Damien
France, Paris
Hôpital Necker Enfants Malades
Li, Xiaoxia
United States, Cleveland
Cleveland Clinic Foundation
Geissmann, Frédéric
France, Paris
Université Paris Cité
France, Paris
Inserm
Vivier, Éric
France, Paris
Cnrs Centre National de la Recherche Scientifique
Máródi, László D.R.
Hungary, Debrecen
Általános Orvostudományi Kar
Garty, Ben Zion
Israel, Petah Tiqwa
Schneider Childrens Medical Center Israel
Chapel, Helen M.
United Kingdom, Oxford
John Radcliffe Hospital
Rodríguez-Gallego, Carlos
Spain, Las Palmas de Gran Canaria
Hospital de Gran Canaria Dr. Negrin
Bossuyt, Xavier
Belgium, Leuven
Ku Leuven– University Hospital Leuven
Abel, Laurent
France, Paris
L'institut Des Maladies Génétiques Imagine
France, Paris
Université Paris Cité
Puel, Anne
France, Paris
L'institut Des Maladies Génétiques Imagine
France, Paris
Université Paris Cité
Casanova, Jean Laurent
France, Paris
L'institut Des Maladies Génétiques Imagine
France, Paris
Université Paris Cité
France, Paris
Hôpital Necker Enfants Malades
Statistics
Citations: 396
Authors: 37
Affiliations: 26
Identifiers
Doi:
10.1084/jem.20070628
ISSN:
00221007
e-ISSN:
00221007
Research Areas
Maternal And Child Health