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

作者:Joller Nicole; Weber Stefan S; Mueller Andreas J; Spoerri Roman; Selchow Petra; Sander Peter; Hilbi Hubert; Oxenius Annette*
来源:Proceedings of the National Academy of Sciences of the United States of America, 2010, 107(47): 20441-20446.
DOI:10.1073/pnas.1013827107

摘要

The protective effect of antibodies (Abs) is generally attributed to neutralization or complement activation. Using Legionella pneumophila and Mycobacterium bovis bacillus Calmette-Guerin 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.