DOI: 10.1084/jem.20070628. Selective predisposition to bacterial infections in IRAK-4–deficient children: IRAK-4–dependent TLRs are otherwise redundant in protective immunity

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

10.1084/jem.20070628

Crossref journal-article

Rockefeller University Press

The Journal of Experimental Medicine (291)

Abstract

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)-a/b 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.

Bibliography

Ku, C.-L., von Bernuth, H., Picard, C., Zhang, S.-Y., Chang, H.-H., Yang, K., Chrabieh, M., Issekutz, A. C., Cunningham, C. K., Gallin, J., Holland, S. M., Roifman, C., Ehl, S., Smart, J., Tang, M., Barrat, F. J., Levy, O., McDonald, D., Day-Good, N. K., â¦ Casanova, J.-L. (2007). Selective predisposition to bacterial infections in IRAK-4âdeficient children: IRAK-4âdependent TLRs are otherwise redundant in protective immunity. The Journal of Experimental Medicine, 204(10), 2407â2422.

Authors 37

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

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Dates

Type	When
Created	17 years, 11 months ago (Sept. 24, 2007, 8:44 p.m.)
Deposited	2 years, 1 month ago (July 25, 2023, 12:35 p.m.)
Indexed	2 weeks, 1 day ago (Aug. 12, 2025, 5:40 p.m.)
Issued	17 years, 11 months ago (Sept. 24, 2007)
Published	17 years, 11 months ago (Sept. 24, 2007)
Published Online	17 years, 11 months ago (Sept. 24, 2007)
Published Print	17 years, 10 months ago (Oct. 1, 2007)

Funders 0

None

BibTeX

@article{Ku_2007, title={Selective predisposition to bacterial infections in IRAK-4–deficient children: IRAK-4–dependent TLRs are otherwise redundant in protective immunity}, volume={204}, ISSN={0022-1007}, url={http://dx.doi.org/10.1084/jem.20070628}, DOI={10.1084/jem.20070628}, number={10}, journal={The Journal of Experimental Medicine}, publisher={Rockefeller University Press}, author={Ku, Cheng-Lung and von Bernuth, Horst and Picard, Capucine and Zhang, Shen-Ying and Chang, Huey-Hsuan and Yang, Kun and Chrabieh, Maya and Issekutz, Andrew C. and Cunningham, Coleen K. and Gallin, John and Holland, Steven M. and Roifman, Chaim and Ehl, Stephan and Smart, Joanne and Tang, Mimi and Barrat, Franck J. and Levy, Ofer and McDonald, Douglas and Day-Good, Noorbibi K. and Miller, Richard and Takada, Hidetoshi and Hara, Toshiro and Al-Hajjar, Sami and Al-Ghonaium, Abdulaziz and Speert, David and Sanlaville, Damien and Li, Xiaoxia and Geissmann, Frédéric and Vivier, Eric and Maródi, László and Garty, Ben-Zion and Chapel, Helen and Rodriguez-Gallego, Carlos and Bossuyt, Xavier and Abel, Laurent and Puel, Anne and Casanova, Jean-Laurent}, year={2007}, month=sep, pages={2407–2422} }

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