Recently, three human primary immunodeficiencies associated with impaired TLR signalling were described. Anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID), either X-linked recessive or autosomal dominant, is caused by hypomorphic mutations in NEMO or hypermorphic mutation in IKBA, respectively, both involved in nuclear factor-κB (NF-κB) activation. These patients present with abnormal development of ectoderm-derived structures and suffer from a broad spectrum of infectious diseases. In vitro studies of the patients' cells showed an impaired, but not abolished, NF-κB activation in response to a large set of stimuli, including TLR agonists. More recently, patients with autosomal recessive amorphic mutations in IRAK4 have been reported, presenting no developmental defect and a more restricted spectrum of infectious diseases, mostly caused by pyogenic encapsulated bacteria, principally, but not exclusively Gram-positive. In vitro studies carried out with these patients' cells showed a specific impairment of the Toll—interleukin-1 receptor (TIR)—interleukin-1 receptor associated kinase (IRAK) signalling pathway. NF-κB- and mitogen activated protein kinase (MAPK) pathways are impaired in response to all TIR agonists tested. These data, therefore, suggest that TLRs play a critical role in host defence against pyogenic bacteria, but may be dispensable or redundant for immunity to most other infectious agents in humans.

EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/LymphedemaV1/Data/France/Analysis

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{{Explor lien
   |wiki=    Wicri/Sante
   |area=    LymphedemaV1
   |flux=    France
   |étape=   Analysis
   |type=    RBID
   |clé=     ISTEX:DF17C65BA99C27741EA602CB05AFF18080C6662D
   |texte=   Heritable defects of the human TLR signalling pathways
}}