Sweet Signals

Sci. Signal.  21 Feb 2012:
Vol. 5, Issue 212, pp. ec54
DOI: 10.1126/scisignal.2002973

When the bacterium Salmonella enterica serovar Typhimurium infects a cell, it enters a vesicle called the Salmonella-containing vacuole (SCV), from which it secretes effector proteins into the host cytosol to modulate the immune response. Such activity damages the SCV, which enables some bacteria to escape and replicate in the cytosol (see commentary by Huang and Brumell). Damage to the SCV stimulates components of the autophagy machinery, such as p62 and NDP52, to target the exposed bacteria, resulting in formation of an autophagosome around the SCV and destruction of the bacteria. Thurston et al. investigated a role for galectins, lectins that are best known to bind to glycans extracellularly, in stimulating autophagy in Salmonella-infected HeLa cells. About 10% of S. Typhyimurium were coated with various galectins within 1 hour of infection and were associated with lysosomes. Knockdown of galectin 8, but not other galectins, resulted in increased proliferation of bacteria compared with that in control cells. Galectin 8 physically associated with NDP52 in vitro, and many SCVs in infected HeLa cells contained both galectin 8 and NDP52. Recruitment of galectin 8 to damaged SCVs did not depend on Salmonella components, but on the exposure of host glycans within the vesicle membrane. Indeed, osmotic damage of endosomes or lysosomes in uninfected cells also resulted in the recruitment of galectin 8, which was dependent on its N-terminal carbohydrate-recognition domain. Galectins 3, 8, and 9 also accumulated on other types of bacteria in infected cells. Whereas binding of NDP52 to galectin 8–coated bacteria occurred early in infection, binding of NDP52 to ubiquitinated bacteria, a previously characterized mechanism that triggers an autophagic response, occurred at later time points. Together, these data suggest that galectin 8 provides an early alternative response to infection of cells by bacteria by sensing damage of vesicular membranes and stimulating the autophagic response.

T. L. M. Thurston, M. P. Wandel, N. von Muhlinen, Á. Foeglein, F. Randow, Galectin 8 targets damaged vesicles for autophagy to defend cells against bacterial invasion. Nature 482, 414–418 (2012). [PubMed]

J. Huang, J. H. Brumell, A sweet way of sensing danger. Nature 482, 316–317 (2012). [Online Journal]