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Infection and Immunity, March 2002, p. 1657-1663, Vol. 70, No. 3
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.3.1657-1663.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

The Dot/Icm Type IV Secretion System of Legionella pneumophila Is Essential for the Induction of Apoptosis in Human Macrophages

Steven D. Zink,1 Lisa Pedersen,1 Nicholas P. Cianciotto,2 and Yousef Abu Kwaik1*

Department of Microbiology and Immunology, University of Kentucky Chandler Medical Center, Lexington, Kentucky 40536-0084,1 Department of Microbiology and Immunology, Northwestern University Medical School, Chicago, Illinois 606112

Received 15 October 2001/ Returned for modification 4 December 2001/ Accepted 17 December 2001

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.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, College of Medicine, Chandler Medical Center, MS408, University of Kentucky, 800 Rose St., Lexington, KY 40536. Phone: (859) 323-3873. Fax: (859) 257-8994. E-mail: yabukw{at}uky.edu.

Infection and Immunity, March 2002, p. 1657-1663, Vol. 70, No. 3
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.3.1657-1663.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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