Lysosomal Degradation Is Required for Sustained Phagocytosis of Bacteria by Macrophages

Publication date: Available online 1 June 2017
Source:Cell Host & Microbe
Author(s): Ching-On Wong, Steven Gregory, Hongxiang Hu, Yufang Chao, Victoria E. Sepúlveda, Yuchun He, David Li-Kroeger, William E. Goldman, Hugo J. Bellen, Kartik Venkatachalam
Clearance of bacteria by macrophages involves internalization of the microorganisms into phagosomes, which are then delivered to endolysosomes for enzymatic degradation. These spatiotemporally segregated processes are not known to be functionally coupled. Here, we show that lysosomal degradation of bacteria sustains phagocytic uptake. In Drosophila and mammalian macrophages, lysosomal dysfunction due to loss of the endolysosomal Cl⁻ transporter ClC-b/CLCN7 delayed degradation of internalized bacteria. Unexpectedly, defective lysosomal degradation of bacteria also attenuated further phagocytosis, resulting in elevated bacterial load. Exogenous application of bacterial peptidoglycans restored phagocytic uptake in the lysosomal degradation-defective mutants via a pathway requiring cytosolic pattern recognition receptors and NF-κB. Mammalian macrophages that are unable to degrade internalized bacteria also exhibit compromised NF-κB activation. Our findings reveal a role for phagolysosomal degradation in activating an evolutionarily conserved signaling cascade, which ensures that continuous uptake of bacteria is preceded by lysosomal degradation of microbes.

Graphical abstract

Teaser

Macrophages clear bacteria by phagosomal internalization and subsequent lysosomal degradation of the microbes. Wong et al. find that defective lysosomal degradation attenuates further phagocytosis, resulting in elevated bacterial load. Cytosolic pattern recognition receptors and NF-κB signal to couple phagolysosomal degradation to sustained phagocytic bacterial clearance.


http://ift.tt/2rAc9Bl