Selective predisposition to bacterial infections in IRAK-4-deficient children: IRAK-4-dependent TLRs are otherwise redundant in protective immunity.
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 lar...
| Hlavní autoři: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Médium: | Journal article |
| Jazyk: | English |
| Vydáno: |
2007
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| _version_ | 1826266125901496320 |
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| author | Ku, C von Bernuth, H Picard, C Zhang, S Chang, H Yang, K Chrabieh, M Issekutz, A Cunningham, C Gallin, J Holland, S Roifman, C Ehl, S Smart, J Tang, M Barrat, F Levy, O McDonald, D Day-Good, N Miller, R Takada, H Hara, T Al-Hajjar, S Al-Ghonaium, A Speert, D |
| author_facet | Ku, C von Bernuth, H Picard, C Zhang, S Chang, H Yang, K Chrabieh, M Issekutz, A Cunningham, C Gallin, J Holland, S Roifman, C Ehl, S Smart, J Tang, M Barrat, F Levy, O McDonald, D Day-Good, N Miller, R Takada, H Hara, T Al-Hajjar, S Al-Ghonaium, A Speert, D |
| author_sort | Ku, C |
| collection | OXFORD |
| 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)-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. |
| first_indexed | 2024-03-06T20:34:12Z |
| format | Journal article |
| id | oxford-uuid:3212de8b-f06a-4a2b-847c-13a67c7b113a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:34:12Z |
| publishDate | 2007 |
| record_format | dspace |
| spelling | oxford-uuid:3212de8b-f06a-4a2b-847c-13a67c7b113a2022-03-26T13:11:46ZSelective predisposition to bacterial infections in IRAK-4-deficient children: IRAK-4-dependent TLRs are otherwise redundant in protective immunity.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3212de8b-f06a-4a2b-847c-13a67c7b113aEnglishSymplectic Elements at Oxford2007Ku, Cvon Bernuth, HPicard, CZhang, SChang, HYang, KChrabieh, MIssekutz, ACunningham, CGallin, JHolland, SRoifman, CEhl, SSmart, JTang, MBarrat, FLevy, OMcDonald, DDay-Good, NMiller, RTakada, HHara, TAl-Hajjar, SAl-Ghonaium, ASpeert, DHuman 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. |
| spellingShingle | Ku, C von Bernuth, H Picard, C Zhang, S Chang, H Yang, K Chrabieh, M Issekutz, A Cunningham, C Gallin, J Holland, S Roifman, C Ehl, S Smart, J Tang, M Barrat, F Levy, O McDonald, D Day-Good, N Miller, R Takada, H Hara, T Al-Hajjar, S Al-Ghonaium, A Speert, D Selective predisposition to bacterial infections in IRAK-4-deficient children: IRAK-4-dependent TLRs are otherwise redundant in protective immunity. |
| title | Selective predisposition to bacterial infections in IRAK-4-deficient children: IRAK-4-dependent TLRs are otherwise redundant in protective immunity. |
| title_full | Selective predisposition to bacterial infections in IRAK-4-deficient children: IRAK-4-dependent TLRs are otherwise redundant in protective immunity. |
| title_fullStr | Selective predisposition to bacterial infections in IRAK-4-deficient children: IRAK-4-dependent TLRs are otherwise redundant in protective immunity. |
| title_full_unstemmed | Selective predisposition to bacterial infections in IRAK-4-deficient children: IRAK-4-dependent TLRs are otherwise redundant in protective immunity. |
| title_short | Selective predisposition to bacterial infections in IRAK-4-deficient children: IRAK-4-dependent TLRs are otherwise redundant in protective immunity. |
| title_sort | selective predisposition to bacterial infections in irak 4 deficient children irak 4 dependent tlrs are otherwise redundant in protective immunity |
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