Home
/
Data resources
/
Literature
/
16940169
NF-kappaB translocation prevents host cell death after low-dose challenge by Legionella pneumophila.

J Exp Med, 2006/9/04;203(9):2177-89.

Losick VP[1], Isberg RR

Affiliations

PMID: 16940169

Impact factor: 17.579

Abstract
Legionella pneumophila, the causative agent of Legionnaires' disease, grows within macrophages and manipulates target cell signaling. Formation of a Legionella-containing replication vacuole requires the function of the bacterial type IV secretion system (Dot/Icm), which transfers protein substrates into the host cell cytoplasm. A global microarray analysis was used to examine the response of human macrophage-like U937 cells to low-dose infections with L. pneumophila. The most striking change in expression was the Dot/Icm-dependent up-regulation of antiapoptotic genes positively controlled by the transcriptional regulator nuclear factor kappaB (NF-kappaB). Consistent with this finding, L. pneumophila triggered nuclear localization of NF-kappaB in human and mouse macrophages in a Dot/Icm-dependent manner. The mechanism of activation at low-dose infections involved a signaling pathway that occurred independently of the Toll-like receptor adaptor MyD88 and the cytoplasmic sensor Nod1. In contrast, high multiplicity of infection conditions caused a host cell response that masked the unique Dot/Icm-dependent activation of NF-kappaB. Inhibition of NF-kappaB translocation into the nucleus resulted in premature host cell death and termination of bacterial replication. In the absence of one antiapoptotic protein, plasminogen activator inhibitor-2, host cell death increased in response to L. pneumophila infection, indicating that induction of antiapoptotic genes is critical for host cell survival.
MeSH terms
Active Transport, Cell Nucleus; Adaptor Proteins, Signal Transducing; Animals; Apoptosis; Bacterial Proteins; Cell Line, Tumor; Cell Survival; Gene Expression Profiling; Humans; Legionella pneumophila; Macrophages; Mice; Myeloid Differentiation Factor 88; Nod1 Signaling Adaptor Protein; Oligonucleotide Array Sequence Analysis; Plasminogen Activator Inhibitor 2; Recombinant Fusion Proteins; Signal Transduction; Transcription Factor RelA
More resources
EndNote: Download