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PMID: 11854262 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

The Dot/Icm type IV secretion system of Legionella pneumophila is essential for the induction of apoptosis in human macrophages.

Infection and immunity ·Vol. 70 ·No. 3 ·2002-03-00 ·Pages 1657-63

Zink SD, Pedersen L, Cianciotto NP, Abu-Kwaik Y

Abstract

We have previously shown that Legionella pneumophila induces caspase 3-dependent apoptosis in mammalian cells during early stages of infection. In this report, we show that nine L. pneumophila strains with mutations in the dotA, dotDCB, icmT, icmGCD, and icmJB loci are completely defective in the induction of apoptosis, in addition to their severe defects in intracellular replication and pore formation-mediated cytotoxicity. Importantly, all nine dot/icm mutants were complemented for all their defective phenotypes with the respective wild-type loci. We show that the role of the Dot/Icm type IV secretion system in the induction of apoptosis is independent of the RtxA toxin, the dot/icm-regulated pore-forming toxin, and the type II secretion system. However, the pore-forming toxin, which is triggered upon entry into the postexponential growth phase, enhances the ability of L. pneumophila to induce apoptosis. Our data provide the first example of the role of a type IV secretion system of a bacterial pathogen in the induction of apoptosis in the host cell.

MeSH Terms
Apoptosis Bacterial Proteins/metabolism Enzymes/metabolism Humans Legionella pneumophila/genetics,metabolism,pathogenicity Macrophages/microbiology Mutation U937 Cells
Chemicals
Bacterial Proteins Enzymes
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Zink Steven D
Department of Microbiology and Immunology, University of Kentucky Chandler Medical Center, Lexington, Kentucky 40536-0084, USA.
Pedersen Lisa
Cianciotto Nicholas P
Abu-Kwaik Yousef
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Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
DOI
10.1128/IAI.70.3.1657-1663.2002
Published
2002-03-00
Pages
1657-63
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC127815
Subset
IM
Grants
NIAID NIH HHS · R01 AI043965 · United States
NIAID NIH HHS · R01 AI043987 · United States
NIAID NIH HHS · R01AI43965 · United States
NIAID NIH HHS · R01AI43987 · United States
External Links
PubMed source DOI: 10.1128/IAI.70.3.1657-1663.2002 PMC Full Text View journal details
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