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Murine Nod1 but not its human orthologue mediates innate immune detection of tracheal cytotoxin
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Murine Nod1 but not its human orthologue mediates innate immune detection of tracheal cytotoxin
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Murine Nod1 but not its human orthologue mediates innate immune detection of tracheal cytotoxin
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Journal Article
Murine Nod1 but not its human orthologue mediates innate immune detection of tracheal cytotoxin
2005
Overview
Tracheal cytotoxin (TCT) was originally described as the minimal effector that was able to reproduce the cytotoxic response of
Bordetella pertussis
on ciliated epithelial cells. This molecule triggers pleiotropic effects such as immune stimulation or slow‐wave sleep modulation. Further characterization identified TCT as a specific diaminopimelic acid (DAP)‐containing muropeptide, GlcNAc‐(anhydro)MurNAc‐
L
‐Ala‐
D
‐Glu‐
meso
DAP‐
D
‐Ala. Here, we show that the biological activity of TCT depends on Nod1, an intracellular sensor of bacterial peptidoglycan. However, Nod1‐dependent detection of TCT was found to be host specific, as human Nod1 (hNod1) poorly detected TCT, whereas mouse Nod1 (mNod1) did so efficiently. More generally, hNod1 required a tripeptide (
L
‐Ala‐
D
‐Glu‐
meso
DAP) for efficient sensing of peptidoglycan, whereas mNod1 detected a tetrapeptide structure (
L
‐Ala‐
D
‐Glu‐
meso
DAP‐
D
‐Ala). In murine macrophages, TCT stimulated cytokine secretion and NO production through Nod1. Finally,
in vivo
, injection of the tetrapeptide structure in mice triggered a transient yet strong release of cytokines into the bloodstream and the maturation of macrophages, in a Nod1‐dependent manner. This study thereby identifies Nod1 as the long sought after sensor of TCT in mammals.
Publisher
John Wiley & Sons, Ltd,Nature Publishing Group UK,Springer Nature B.V
Subject
Adaptor Proteins, Signal Transducing - metabolism
/ Animals
/ Cytotoxins - administration & dosage
/ Humans
/ Leukocytes, Mononuclear - drug effects
/ Macrophage Activation - drug effects
/ Macrophages, Peritoneal - drug effects
/ Mammals
/ Mice
/ Nod1 Signaling Adaptor Protein
/ Peptidoglycan - pharmacology
/ Sleep
