Journal article
Primary Immunodeficiency to pneumococcal infection due to a defect in Toll-like receptor signaling
The Journal of Pediatrics, Vol.144(4), pp.512-518
2004
Abstract
Objective: The role of human Toll-like receptors (TLRs) in initiating protective immune responses in vivo is not well understood. We investigated the role of TLR signaling in defense against infection in a 3-year-old boy with a severe defect resulting in recurrent Streptococcus pneumoniae bacteremia. Methods: After classic immunodeficiencies were ruled out, the patient's mononuclear cells, macrophages, and dendritic cells (DCs) were studied. TLR signaling responses to a range of TLR- and interleukin-1 receptor (IL-1R)-specific agonists were investigated pre- and posttranscriptionally by measuring NF-κB translocation and cytokine mRNA and protein expression. Results: The patient's monocytic cells were profoundly deficient in cytokine production in response to a range of microbial-derived TLR agonists and to recombinant IL-1β or IL-18. Lipopolysaccharide (LPS)-induced translocation of NF-κB p50 and p65 and the kinetics of LPS-induced cytokine mRNA transcription were normal except for IL-6 and IL-12p40, which were poorly transcribed. Despite deficient responses to TLR agonists by the patient's DCs and B cells, CD40L responses were normal. Conclusions: We describe a patient with deficient TLR-mediated cytokine production with intact interleukin receptor-associated kinase (IRAK)-4 expression, NF-κB translocation, and enhanced susceptibility to infection. This patient demonstrates that TLR signaling, in the presence of intact antibody responses, may be a nonredundant requirement for defense against pyogenic infections.
Details
- Title
- Primary Immunodeficiency to pneumococcal infection due to a defect in Toll-like receptor signaling
- Authors/Creators
- A.J. Currie (Author/Creator)D.J. Davidson (Author/Creator)G.S.D. Reid (Author/Creator)S. Bharya (Author/Creator)K.L. MacDonald (Author/Creator)R.S. Devon (Author/Creator)D.P. Speert (Author/Creator)
- Publication Details
- The Journal of Pediatrics, Vol.144(4), pp.512-518
- Publisher
- Elsevier
- Identifiers
- 991005542501707891
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
UN Sustainable Development Goals (SDGs)
This output has contributed to the advancement of the following goals:
Source: InCites
Metrics
34 Record Views
InCites Highlights
These are selected metrics from InCites Benchmarking & Analytics tool, related to this output
- Collaboration types
- Domestic collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.6 Immunology
- 1.6.609 Toll-like Receptors
- Web Of Science research areas
- Pediatrics
- ESI research areas
- Clinical Medicine