[HTML][HTML] Signaling pathways and genes that inhibit pathogen-induced macrophage apoptosis—CREB and NF-κB as key regulators

JM Park, FR Greten, A Wong, RJ Westrick, JSC Arthur… - Immunity, 2005 - cell.com
JM Park, FR Greten, A Wong, RJ Westrick, JSC Arthur, K Otsu, A Hoffmann, M Montminy…
Immunity, 2005cell.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 …
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.
cell.com