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Wong, C.O., Gregory, S., Hu, H., Chao, Y., Sepúlveda, V.E., He, Y., Li-Kroeger, D., Goldman, W.E., Bellen, H.J., Venkatachalam, K. (2017). Lysosomal Degradation Is Required for Sustained Phagocytosis of Bacteria by Macrophages.  Cell Host Microbe 21(6): 719--730.
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Research paper

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.

PubMed ID
PubMed Central ID
PMC5540652 (PMC) (EuropePMC)
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    Parent Publication
    Publication Type
    Cell Host Microbe
    Cell Host & Microbe
    Publication Year
    1931-3128 1934-6069
    Data From Reference
    Aberrations (1)
    Alleles (30)
    Genes (18)
    Polypeptides (1)
    Natural transposons (1)
    Insertions (8)
    Experimental Tools (5)
    Transgenic Constructs (23)