NF-κB-mediated self defense of macrophages faced with bacteria

Abstract

NF-κB is a ubiquitous transcription factor that is extensively exploited by immune cells involved in host defense mechanisms. Macrophages participate in the first line of defense against microorganisms, but little is known about whether and how NF-κB is involved in the handling of microbes by macrophages. To explore this issue, NF-κB-inactive macrophages, NIKMACNR, were created by overexpression of a super-repressor mutant of IκBα. When co-cultured with Escherichia coli, the NIKMACNR macrophages exhibited impairment of bactercidal activity. Microscopic analysis revealed that NIKMACNR cells faced with bacteria underwent rapid and fulminant apoptosis. Similary, NIKMACNR macrophages cultured in the presence of a bacterial component, lipopolysaccharide, showed dramatic apoptosis. Inhibition of RNA synthesis or protein synthesis failed to block the apoptosis of NIKMACNR cells, indicating that macrophages possess a pre-existing, apoptotic pathway that can be triggered by bacteria. Apoptosis was not observed in NIKMACNR macrophages exposed to non-microbial stimuli including phorbol ester and opsonized zymosan. However, NIKMACNR cells were more susceptible to apoptosis triggered by TNF-α and reactive oxygen intermediates, both of which are produced abundantly by macrophages when faced with bacteria. These data suggest a critical role for NF-κB in the survival of macrophages at the site of bacterial infection.