Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 3346K) PDF+supp data (5289K) PPT slides of all figures Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Goldszmid, R. S. Articles by Sher, A. Search for Related Content PubMed PubMed Citation Articles by Goldszmid, R. S. Articles by Sher, A. Related Collections Related Article Social Bookmarking                            What's this?

¹ Immunobiology Section, Laboratory of Parasitic Diseases and ² Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
³ Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205
⁴ Genentech, Inc., South San Francisco, CA 94080

CORRESPONDENCE Romina S. Goldszmid: rgoldszmid{at}niaid.nih.gov OR Alan Sher: asher{at}niaid.nih.gov

Toxoplasma gondii tachyzoites infect host cells by an active invasion process leading to the formation of a specialized compartment, the parasitophorous vacuole (PV). PVs resist fusion with host cell endosomes and lysosomes and are thus distinct from phagosomes. Because the parasite remains sequestered within the PV, it is unclear how T. gondii–derived antigens (Ag’s) access the major histocompatibility complex (MHC) class I pathway for presentation to CD8⁺ T cells. We demonstrate that recruitment of host endoplasmic reticulum (hER) to the PV in T. gondii–infected dendritic cells (DCs) directly correlates with cross-priming of CD8⁺ T cells. Furthermore, we document by immunoelectron microscopy the transfer of hER components into the PV, a process indicative of direct fusion between the two compartments. In strong contrast, no association between hER and phagosomes or Ag presentation activity was observed in DCs containing phagocytosed live or dead parasites. Importantly, cross-presentation of parasite-derived Ag in actively infected cells was blocked when hER retrotranslocation was inhibited, indicating that the hER serves as a conduit for the transport of Ag between the PV and host cytosol. Collectively, these findings demonstrate that pathogen-driven hER–PV interaction can serve as an important mechanism for Ag entry into the MHC class I pathway and CD8⁺ T cell cross-priming.

This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Article

Toxo has a ticket to ride

Amy Maxmen
J. Exp. Med. 2009 206: 260. [Full Text] [PDF]

This article has been cited by other articles:

• Bushkin, G. G., Ratner, D. M., Cui, J., Banerjee, S., Duraisingh, M. T., Jennings, C. V., Dvorin, J. D., Gubbels, M.-J., Robertson, S. D., Steffen, M., O'Keefe, B. R., Robbins, P. W., Samuelson, J. (2010). Suggestive Evidence for Darwinian Selection against Asparagine-Linked Glycans of Plasmodium falciparum and Toxoplasma gondii. Eukaryot Cell 9: 228-241 [Abstract] [Full Text]  
• Lee, B.-Y., Jethwaney, D., Schilling, B., Clemens, D. L., Gibson, B. W., Horwitz, M. A. (2010). The Mycobacterium bovis Bacille Calmette-Guerin Phagosome Proteome. Mol. Cell. Proteomics 9: 32-53 [Abstract] [Full Text]  
• Goldszmid, R. S., Coppens, I., Lev, A., Caspar, P., Mellman, I., Sher, A. (2009). Host ER-parasitophorous vacuole interaction provides a route of entry for antigen cross-presentation in Toxoplasma gondii-infected dendritic cells. JCB 184: i4-i4 [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS