One major difference between our studies and others that studied the interaction between autophagy and L. monocytogenes is that we used primary cultures of BMDMs lacking Atg5, while others used transfected RAW macrophage-like cells and atg5 2/2 MEFs, respectively [23, 24, 34] . Additionally, we examined phagosomal escape much earlier during infection. The majority of wildtype L. monocytogenes escape the vacuole within the first 30 minutes following entry, however Py et al. (2007) assayed escape at four hours post-infection [44] . Since L. monocytogenes begin to spread from cell to cell as early as three hours post-infection and phospholipase mutants have a known defect in escape from a secondary vacuole, it is possible that the defect in growth observed by Py et al. (2007) was due to a defect in escape from vacuoles of secondarily infected cells [13, 45, 46] Autophagy plays a role in cellular homeostasis. For example, smooth ER, excess peroxisomes, damaged mitochondria and rough ER have been shown to be selectively targeted and removed from cells by the autophagic machinery [47] [48] [49] [50] . We propose that some or all of these organelles are targeted by autophagy due to membrane damage. For example, chemically damaged mitochondria are selectively targeted and removed by autophagy [49] . Selective removal is thought to be due to the disruption of the inner membrane by pores which occurs upon depolarization, a signal which may be similar to pore formation due to cytolysin expression [49] . Our hypothesis is further supported by two reports showing that two pore forming toxins secreted by extracellular pathogens, Vibrio cholerae cytolysin (VCC) and the vacuolating cytotoxin from Helicobacter pylori (VacA), also induce autophagy in the absence of infection [51] [52] [53] . Autophagic bodies were identified inside of cells exposed to VCC [52] . Similarly, we noted non-specific induction of autophagy (diffuse puncta formation), when LC3-GFP BMDMs were exposed to increasing concentrations of extracellular LLO (data not shown). Further autophagic induction in response to VacA was blocked when the channel forming activity of the toxin was inhibited [53] . Therefore, autophagy may be a general response to membrane damage, and as a result may have evolved as a mechanism to recognize and target intracellular pathogens.