HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Tamilselvam, B. Articles by Daefler, S. PubMed PubMed Citation Articles by Tamilselvam, B. Articles by Daefler, S.

Francisella Targets Cholesterol-Rich Host Cell Membrane Domains for Entry into Macrophages¹

Mount Sinai School of Medicine, New York, NY 10570

Francisella tularensis is a pathogen optimally adapted to efficiently invade its respective host cell and to proliferate intracellularly. We investigated the role of host cell membrane microdomains in the entry of F. tularensis subspecies holarctica vaccine strain (F. tularensis live vaccine strain) into murine macrophages. F. tularensis live vaccine strain recruits cholesterol-rich lipid domains ("lipid rafts") with caveolin-1 for successful entry into macrophages. Interference with lipid rafts through the depletion of plasma membrane cholesterol, through induction of raft internalization with choleratoxin, or through removal of raft-associated GPI-anchored proteins by treatment with phosphatidylinositol phospholipase C significantly inhibited entry of Francisella and its intracellular proliferation. Lipid raft-associated components such as cholesterol and caveolin-1 were incorporated into Francisella-containing vesicles during entry and the initial phase of intracellular trafficking inside the host cell. These findings demonstrate that Francisella requires cholesterol-rich membrane domains for entry into and proliferation inside macrophages.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by U.S. Public Health Service Grant P01 AI55637.

² Address correspondence and reprint requests to Dr. Simon Daefler, Mount Sinai School of Medicine, One Gustave Levy Place, New York, NY 10570. E-mail address: simon.daefler{at}mssm.edu

³ Abbreviations used in this paper: LVS, live vaccine strain; Cav1-GFP, fusion of GFP to caveolin-1; MβCD, methyl-β-cyclodextrin; MOI, multiplicity of infection; PI-PLC, phosphatidylinositol phospholipase C; SRA, scavenger receptor class A.