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Galectin 8 targets damaged vesicles for autophagy to defend cells against bacterial invasion

Abstract

Autophagy defends the mammalian cytosol against bacterial infection1,2,3. Efficient pathogen engulfment is mediated by cargo-selecting autophagy adaptors that rely on unidentified pattern-recognition or danger receptors to label invading pathogens as autophagy cargo, typically by polyubiquitin coating4,5,6,7,8,9. Here we show in human cells that galectin 8 (also known as LGALS8), a cytosolic lectin, is a danger receptor that restricts Salmonella proliferation. Galectin 8 monitors endosomal and lysosomal integrity and detects bacterial invasion by binding host glycans exposed on damaged Salmonella-containing vacuoles. By recruiting NDP52 (also known as CALCOCO2), galectin 8 activates antibacterial autophagy. Galectin-8-dependent recruitment of NDP52 to Salmonella-containing vesicles is transient and followed by ubiquitin-dependent NDP52 recruitment. Because galectin 8 also detects sterile damage to endosomes or lysosomes, as well as invasion by Listeria or Shigella, we suggest that galectin 8 serves as a versatile receptor for vesicle-damaging pathogens. Our results illustrate how cells deploy the danger receptor galectin 8 to combat infection by monitoring endosomal and lysosomal integrity on the basis of the specific lack of complex carbohydrates in the cytosol.

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Figure 1: Galectin 8 responds to infection by S. Typhimurium and restricts bacterial proliferation.
Figure 2: Galectin 8 binds NDP52.
Figure 3: Galectin 8 is a danger receptor that senses cytosolic host glycans and recruits NDP52 to restrict Salmonella proliferation.
Figure 4: The antibacterial effect of galectin 8 is mediated by autophagy.

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Acknowledgements

We thank J. Kendrick-Jones (MRC Laboratory of Molecular Biology), A. Geerlof (European Molecular Biology Laboratory Heidelberg), N. Mizushima (Tokyo University) and P. Stanley (Albert Einstein College of Medicine) for kindly sharing reagents.

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T.L.M.T., M.P.W., N.v.M., Á.F. and F.R. planned, performed and analysed experiments. T.L.M.T. and F.R. designed the overall research. F.R. wrote the manuscript.

Corresponding author

Correspondence to Felix Randow.

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The authors declare no competing financial interests.

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Thurston, T., Wandel, M., von Muhlinen, N. et al. Galectin 8 targets damaged vesicles for autophagy to defend cells against bacterial invasion. Nature 482, 414–418 (2012). https://doi.org/10.1038/nature10744

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