[HTML][HTML] Signaling pathways and genes that inhibit pathogen-induced macrophage apoptosis—CREB and NF-κB as key regulators
Immunity, 2005•cell.com
Certain microbes evade host innate immunity by killing activated macrophages with the help
of virulence factors that target prosurvival pathways. For instance, infection of macrophages
with the TLR4-activating bacterium Bacillus anthracis triggers an apoptotic response due to
inhibition of p38 MAP kinase activation by the bacterial-produced lethal toxin. Other
pathogens induce macrophage apoptosis by preventing activation of NF-κB, which depends
on IκB kinase β (IKKβ). To better understand how p38 and NF-κB maintain macrophage …
of virulence factors that target prosurvival pathways. For instance, infection of macrophages
with the TLR4-activating bacterium Bacillus anthracis triggers an apoptotic response due to
inhibition of p38 MAP kinase activation by the bacterial-produced lethal toxin. Other
pathogens induce macrophage apoptosis by preventing activation of NF-κB, which depends
on IκB kinase β (IKKβ). To better understand how p38 and NF-κB maintain macrophage …
Summary
Certain microbes evade host innate immunity by killing activated macrophages with the help of virulence factors that target prosurvival pathways. For instance, infection of macrophages with the TLR4-activating bacterium Bacillus anthracis triggers an apoptotic response due to inhibition of p38 MAP kinase activation by the bacterial-produced lethal toxin. Other pathogens induce macrophage apoptosis by preventing activation of NF-κB, which depends on IκB kinase β (IKKβ). To better understand how p38 and NF-κB maintain macrophage survival, we searched for target genes whose products prevent TLR4-induced apoptosis and a p38-dependent transcription factor required for their induction. Here we describe key roles for transcription factor CREB, a target for p38 signaling, and the plasminogen activator 2 (PAI-2) gene, a target for CREB, in maintenance of macrophage survival.
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