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Non-apoptotic role of BID in inflammation and innate immunity.
Nature. 2011 Jun 2; 474(7349):96-9
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09 Jun 2011
New Finding
DOI: 10.3410/f.11093956.12052054
This paper is fascinating because it shows yet another link between apoptosis- and inflammation-inducing agents; namely, the authors demonstrate that the pro-apoptotic Bcl-2 family member, Bid, is also an essential player in the induction of inflammation, resulting in the opposite outcome from cell...Continue reading
This paper is fascinating because it shows yet another link between apoptosis- and inflammation-inducing agents; namely, the authors demonstrate that the pro-apoptotic Bcl-2 family member, Bid, is also an essential player in the induction of inflammation, resulting in the opposite outcome from cell death.
Using a genome-wide RNAi screen, the authors identified genes that either positively or negatively influenced interleukin-8 (IL-8) production, many of which are involved in apoptosis. This powerful analysis provides completely new insights into a possible co-evolution of apoptosis and innate immunity pathways
Using a genome-wide RNAi screen, the authors identified genes that either positively or negatively influenced interleukin-8 (IL-8) production, many of which are involved in apoptosis. This powerful analysis provides completely new insights into a possible co-evolution of apoptosis and innate immunity pathways
Disclosures
None declared
Add Comment
Huber B: F1000Prime Recommendation of [Yeretssian G et al., Nature 2011, 474(7349):96-9]. In F1000Prime, 09 Jun 2011; DOI: 10.3410/f.11093956.12052054. F1000Prime.com/11093956#eval12052054
26 Sep 2011
Christoph Borner
F1000 Cell Biology
Center for Biochemistry and Molecular Cell Research,
Freiburg, Germany.
F1000 Cell Biology
Center for Biochemistry and Molecular Cell Research,
Freiburg, Germany.
New Finding
DOI: 10.3410/f.11093956.14653291
The novelty of this manuscript is that it shows an unexpected non-apoptotic role of a classical pro-apoptotic molecule, the BH3-only protein BID. BID is well known as an activator of the Bax/Bak pore, leading to cytochrome c release and caspase activation in both the type II extrinsic and mitochondrial...Continue reading
The novelty of this manuscript is that it shows an unexpected non-apoptotic role of a classical pro-apoptotic molecule, the BH3-only protein BID. BID is well known as an activator of the Bax/Bak pore, leading to cytochrome c release and caspase activation in both the type II extrinsic and mitochondrial intrinsic apoptotic pathways. Here, the authors show that BID also modulates the NOD1 inflammatory response by interacting with NOD1, NOD2 and the IkB kinase (IKK) complex impacting on nuclear factor kappa B (NFkB) and ERK signaling.
Importantly, BID -/- mice do not respond to NOD agonists, and macrophages isolated from these mice produce much fewer pro-inflammatory cytokines. In contrast to apoptosis, where BID requires caspase-8-mediated cleavage for its activation, the pro-inflammatory role of BID is independent of this cleavage but instead seems to need phosphorylation by a yet-unknown protein kinase. This study shows another example that the mechanisms of apoptosis and innate immunity are evolutionarily conserved.
Importantly, BID -/- mice do not respond to NOD agonists, and macrophages isolated from these mice produce much fewer pro-inflammatory cytokines. In contrast to apoptosis, where BID requires caspase-8-mediated cleavage for its activation, the pro-inflammatory role of BID is independent of this cleavage but instead seems to need phosphorylation by a yet-unknown protein kinase. This study shows another example that the mechanisms of apoptosis and innate immunity are evolutionarily conserved.
Disclosures
None declared
Borner C: F1000Prime Recommendation of [Yeretssian G et al., Nature 2011, 474(7349):96-9]. In F1000Prime, 26 Sep 2011; DOI: 10.3410/f.11093956.14653291. F1000Prime.com/11093956#eval14653291
F1000Prime Recommendations, Dissents and Comments for [Yeretssian G et al., Nature 2011, 474(7349):96-9]. In F1000Prime, 22 May 2013; F1000Prime.com/11093956
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Innate immunity is a fundamental defence response that depends on evolutionarily conserved pattern recognition receptors for sensing infections or danger signals. Nucleotide-binding and oligomerization domain (NOD) proteins are cytosolic pattern-recognition receptors of paramount importance in the intestine, and their dysregulation is associated with inflammatory bowel disease. They sense peptidoglycans from commensal microorganisms and pathogens and coordinate signalling events that culminate in the induction of inflammation and anti-microbial responses. However, the signalling mechanisms involved in this process are not fully understood. Here, using genome-wide RNA interference, we identify candidate genes that modulate the NOD1 inflammatory response in intestinal epithelial cells. Our results reveal a significant crosstalk between innate immunity and apoptosis and identify BID, a BCL2 family protein, as a critical component of the inflammatory response. Colonocytes depleted of BID or macrophages from Bid(-/-) mice are markedly defective in cytokine production in response to NOD activation. Furthermore, Bid(-/-) mice are unresponsive to local or systemic exposure to NOD agonists or their protective effect in experimental colitis. Mechanistically, BID interacts with NOD1, NOD2 and the IκB kinase (IKK) complex, impacting NF-κB and extracellular signal-regulated kinase (ERK) signalling. Our results define a novel role of BID in inflammation and immunity independent of its apoptotic function, furthering the mounting evidence of evolutionary conservation between the mechanisms of apoptosis and immunity.
DOI: 10.1038/nature09982
PMID: 21552281
