Is BID required for NOD signalling?

Arising from G. Yeretssian et al. Nature 474, 96–99 (2011)10.1038/nature09982 . Innate immune signalling mediated by the nucleotide-binding and oligomerization domain (NOD) receptors for pathogen-associated constituents regulates the response to intracellular peptidoglycans present in Gram-negative and Gram-positive bacteria. Recently, Yeretssian et al.1 reported that the pro-apoptotic BH3-only BCL2 family member BID is essential for NOD-mediated immune signalling. This was on the basis of their finding that bone marrow-derived macrophages (BMDMs) from Bid−/− mice failed to activate NF-κB and extracellular signal-regulated kinase (ERK), and were unable to secrete inflammatory cytokines after stimulation with NOD ligands, and that BID-deficient mice were also defective in mounting a cytokine response to in vivo challenge with NOD ligands. Using the same strain of Bid−/− mice used by Yeretssian et al.1, we found that the mice responded like wild-type mice to NOD ligands, and that the levels of NF-κB or ERK activation and cytokine secretion from Bid−/− BMDMs were indistinguishable from the wild-type response. We therefore propose that the non-apoptotic role of BID in inflammation and innate immunity should be reassessed.