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Antibodies protect against intracellular bacteria by Fc receptor-mediated lysosomal targeting


Joller, N; Weber, S S; Müller, A J; Spörri, R; Selchow, P; Sander, P; Hilbi, H; Oxenius, A (2010). Antibodies protect against intracellular bacteria by Fc receptor-mediated lysosomal targeting. Proceedings of the National Academy of Sciences of the United States of America (PNAS), 107(47):20441-20446.

Abstract

The protective effect of antibodies (Abs) is generally attributed to neutralization or complement activation. Using Legionella pneumophila and Mycobacterium bovis bacillus Calmette-Guérin as a model, we discovered an additional mechanism of Ab-mediated protection effective against intracellular pathogens that normally evade lysosomal fusion. We show that Fc receptor (FcR) engagement by Abs, which can be temporally and spatially separated from bacterial infection, renders the host cell nonpermissive for bacterial replication and targets the pathogens to lysosomes. This process is strictly dependent on kinases involved in FcR signaling but not on host cell protein synthesis or protease activation. Based on these findings, we propose a mechanism whereby Abs and FcR engagement subverts the strategies by which intracellular bacterial pathogens evade lysosomal degradation.

Abstract

The protective effect of antibodies (Abs) is generally attributed to neutralization or complement activation. Using Legionella pneumophila and Mycobacterium bovis bacillus Calmette-Guérin as a model, we discovered an additional mechanism of Ab-mediated protection effective against intracellular pathogens that normally evade lysosomal fusion. We show that Fc receptor (FcR) engagement by Abs, which can be temporally and spatially separated from bacterial infection, renders the host cell nonpermissive for bacterial replication and targets the pathogens to lysosomes. This process is strictly dependent on kinases involved in FcR signaling but not on host cell protein synthesis or protease activation. Based on these findings, we propose a mechanism whereby Abs and FcR engagement subverts the strategies by which intracellular bacterial pathogens evade lysosomal degradation.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Medical Microbiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Health Sciences > Multidisciplinary
Language:English
Date:2010
Deposited On:22 Feb 2011 09:42
Last Modified:23 Jan 2022 18:35
Publisher:National Academy of Sciences
ISSN:0027-8424
OA Status:Closed
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1073/pnas.1013827107
PubMed ID:21048081
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