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BACKGROUND Streptococcus pneumoniae is a major cause of morbidity and mortality in developed and developing countries. No common genetic determinants of susceptibility have been defined. Mannose-binding lectin (MBL) is a key mediator of innate host immunity that activates the complement pathway and directly opsonises some infectious pathogens. Mutations in(More)
Rationale: Increasing evidence supports a key role for the transcription factor nuclear factor (NF)-␬B in the host response to pneumo-coccal infection. Control of NF-␬B activity is achieved through interactions with the I␬B family of inhibitors, encoded by the genes NFKBIA, NFKBIB, and NFKBIE. Rare NFKBIA mutations cause immuno-deficiency with severe(More)
INTRODUCTION Streptococcus pneumoniae remains a major global health problem and a leading cause of death in children worldwide. The factors that influence development of pneumococcal sepsis remain poorly understood, although increasing evidence points towards a role for genetic variation in the host's immune response. Recent insights from the study of(More)
  • Chiea C Khor, Stephen J Chapman, +31 authors Adrian V S Hill
  • 2007
Toll-like receptors (TLRs) and members of their signaling pathway are important in the initiation of the innate immune response to a wide variety of pathogens 1–3. The adaptor protein Mal (also known as TIRAP), encoded by TIRAP (MIM 606252), mediates downstream signaling of TLR2 and TLR4 (refs. 4–6). We report a case-control study of 6,106 individuals from(More)
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