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

N Joller, SS Weber, AJ Müller… - Proceedings of the …, 2010 - National Acad Sciences
N Joller, SS Weber, AJ Müller, R Spörri, P Selchow, P Sander, H Hilbi, A Oxenius
Proceedings of the National Academy of Sciences, 2010National Acad Sciences
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 …
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.
National Acad Sciences