Genome Biology

, 3:spotlight-20020731-01 | Cite as

Keeping innate immunity at bay

  • Michaela Torkar
Research news


Inflammatory Bowel Disease Innate Immune Response Excessive Production Bacterial Cell Wall Innate Immune Cell 

Toll-like receptors (TLRs) recognize pathogen-associated products, such as components of the bacterial cell wall, and activate macrophages and other innate immune cells through a signaling cascade involving serine/threonine kinases of the IRAK family. Richard Flavell and co-workers from Yale University School of Medicine, New Haven, Connecticut report in 26 July Cell that at least one member of the IRAK family, IRAK-M, is a negative regulator of TLR signaling (Cell 2002, 110:191-202). They suggest IRAK-M controls a balance between the innate immune response and excessive production of cytokines, which can be potentially harmful to the host.

Kobayashi et al. show that lack of IRAK-M causes increased production of inflammatory cytokines, including interleukin-6 and tumor-necrosis factor α, and an enhanced inflammatory response in the gut of IRAK-M-/- mice infected with the Gram-negative pathogen Salmonella typhimurium. IRAK-M-/-macrophages did not develop endotoxin tolerance to the bacterial lipopolysaccharide, a little-understood regulatory mechanism that protects from endotoxic shock. TLR signaling following stimulation of macrophages was enhanced in the absence of IRAK-M, and immunoprecipitations suggested that, in wild-type mice, IRAK-M inhibits the release of activating IRAK kinases from the TLR signaling complex, thereby blocking downstream signaling events.

Kobayashi et al. conclude that the negative regulatory function of IRAK-M may be required for preventing endotoxic shock and immunopathologies such as Crohn's and other inflammatory bowel diseases.


  1. 1.
    Armant MA, Fenton MJ: Toll-like receptors: a family of pattern-recognition receptors in mammals. Genome Biol 3:reviews3011.1-3011.6, []
  2. 2.
    Yale University, []
  3. 3.
    Kobayashi K, Hernandez LD, Galÿn JE, Janeway CA, Medzhitov R, Flavell RA.: IRAK-M is a negative regulator of Toll-like receptor signaling. Cell 2002, 110:191-202., []

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© BioMed Central Ltd 2002

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  • Michaela Torkar

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