Format

Send to

Choose Destination
J Pediatr. 2004 Apr;144(4):512-8.

Primary immunodeficiency to pneumococcal infection due to a defect in Toll-like receptor signaling.

Author information

1
Division of Infectious and Immunological Diseases, British Columbia's Research Institute for Child and Family Health, 950 West 28th Avenue, Vancouver, British Columbia, Canada V5Z 4H4.

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-kappaB 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-1beta or IL-18. Lipopolysaccharide (LPS)-induced translocation of NF-kappaB 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-kappaB 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.

PMID:
15069402
DOI:
10.1016/j.jpeds.2003.10.034
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center