Transcription profiling of responses to TNF-alpha, IL-1beta, peptidoglycan or lipopolysaccharide (TLR2/4 agonists) evaluated at 4 hrs in peripheral blood monocytes (PBM) from the patient bearing the IRAK4 Q293X mutation vs PBM from 5 healthy individuals

ABSTRACT: IL-1R associated kinase-4 (IRAK4) is a key enzyme required for activation of the common Toll-like Receptor (TLR) signaling cascade, which results in the transcription of inflammatory and immunity genes. IRAK-4 deficiency has recently been described as a rare form of innate immunodeficiency. Patients present with pyogenic bacterial infections and bacteraemia, particularly with Gram+ Streptococcus pneumoniae, and isolated PBMC from these patients fail to produce inflammatory cytokines in response to TLR agonists. We embarked on this study for several purposes: (1) to identify defective gene response resulting from IRAK4-deficiency that are responsible for the patients' susceptibility to infection by particular bacteria (2) to identify genetic responses that confer relatively normal immunity in these patients despite having a defect in such a critical component of the innate immune system (3) to gain understanding of the transcriptional regulation of inflammatory genes (4) to gain insight into TLR signal transduction pathways, in particular, the role of IRAK4 in the TLR2 and TLR4 pathways initiated by Gram+ and Gram- bacterial components respectively. Transcriptional responses to TNF-alpha, IL-1beta, peptidoglycan or lipopolysaccharide (TLR2/4 agonists) were evaluated at 4 hrs in peripheral blood monocytes (PBM) from the patient bearing the IRAK4 Q293X mutation compared to PBM from 5 healthy individuals.

ORGANISM(S): Homo sapiens

DISEASE(S): IRAK-4 Q293X mutation

SUBMITTER: Kelly Brown 

PROVIDER: E-FPMI-7 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress