A narrow repertoire of transcriptional modules responsive to pyogenic bacteria is impaired in patients carrying loss-of-function mutations in MYD88 or IRAK4 Academic Article uri icon


MeSH Major

  • Immunologic Deficiency Syndromes
  • Interleukin-1 Receptor-Associated Kinases
  • Mutation
  • Myeloid Differentiation Factor 88


  • Loss of function of the kinase IRAK4 or the adaptor MyD88 in humans interrupts a pathway critical for pathogen sensing and ignition of inflammation. However, patients with loss-of-function mutations in the genes encoding these factors are, unexpectedly, susceptible to only a limited range of pathogens. We employed a systems approach to investigate transcriptome responses following in vitro exposure of patients' blood to agonists of Toll-like receptors (TLRs) and receptors for interleukin 1 (IL-1Rs) and to whole pathogens. Responses to purified agonists were globally abolished, but variable residual responses were present following exposure to whole pathogens. Further delineation of the latter responses identified a narrow repertoire of transcriptional programs affected by loss of MyD88 function or IRAK4 function. Our work introduces the use of a systems approach for the global assessment of innate immune responses and the characterization of human primary immunodeficiencies.

publication date

  • January 2014



  • Academic Article



  • eng

PubMed Central ID

  • PMC4281021

Digital Object Identifier (DOI)

  • 10.1038/ni.3028

PubMed ID

  • 25344726

Additional Document Info

start page

  • 1134

end page

  • 42


  • 15


  • 12