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Infection and Immunity, November 2006, p. 6387-6397, Vol. 74, No. 11
0019-9567/06/$08.00+0     doi:10.1128/IAI.01088-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Cytosolic Entry Controls CD8+-T-Cell Potency during Bacterial Infection{triangledown}

Keith S. Bahjat,1* Weiqun Liu,1 Edward E. Lemmens,1 Stephen P. Schoenberger,2 Daniel A. Portnoy,3 Thomas W. Dubensky Jr.,1 and Dirk G. Brockstedt1

Cerus Corporation, Concord, California,1 Division of Cellular Immunology, La Jolla Institute for Allergy & Immunology, San Diego, California,2 Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California3

Received 11 July 2006/ Returned for modification 4 August 2006/ Accepted 28 August 2006

Interaction with host immunoreceptors during microbial infection directly impacts the magnitude of the ensuing innate immune response. How these signals affect the quality of the adaptive T-cell response remains poorly understood. Utilizing an engineered strain of the intracellular pathogen Listeria monocytogenes that infects cells but fails to escape from the phagosome, we demonstrate the induction of long-lived memory T cells that are capable of secondary expansion and effector function but are incapable of providing protective immunity. We demonstrate that microbial invasion of the cytosol is required for dendritic cell activation and integration of CD40 signaling, ultimately determining the ability of the elicited CD8+-T-cell pool to protect against lethal wild-type L. monocytogenes challenge. These results reveal a crucial role for phagosomal escape, not for delivery of antigen to the class I major histocompatibility complex pathway but for establishing the appropriate cellular context during CD8+-T-cell priming.

* Corresponding author. Mailing address: Cerus Corporation, 2411 Stanwell Drive, Concord, CA 94520. Phone: (925) 288-6120. Fax: (925) 671-9272. E-mail: keith_bahjat{at}cerus.com.

{triangledown} Published ahead of print on 5 September 2006.

Editor: V. J. DiRita

Infection and Immunity, November 2006, p. 6387-6397, Vol. 74, No. 11
0019-9567/06/$08.00+0     doi:10.1128/IAI.01088-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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