L. monocytogenes has been shown to interact with the host autophagic machinery. Rich et al. (2003) reported that approximately 92% of chloramphenicol treated L. monocytogenes were surrounded by double-membrane vacuoles in J774 macrophage-like cells 21 hours post infection. The number of these chloramphenicoltreated bacteria captured by autophagic-like membranes decreased in the presence of autophagy inhibitors [22] . Subsequently, Py et al. (2007) showed that L. monocytogenes induces autophagy, as measured by microtubule associated light chain 3 (LC3) lipidation and colocalization of LC3 with intracellular bacteria. Further, Py et al., (2007) provided evidence that L. monocytogenes replicate more efficiently in autophagy-deficient (atg5 2/2 ) mouse embryonic fibroblasts (MEFs) compared to wild-type MEFs, suggesting that an Atg5-dependent process directly inhibits the replication of wildtype L. monocytogenes in mammalian cells. Using similar assays to test for autophagic induction, Birmingham et al. (2007) demonstrated that RAW 264.7 macrophages transfected with LC3-GFP, exhibited colocalization of transfected LC3-GFP with L. monocytogenes. However, the authors of this study did not observe that wild-type L. monocytogenes grew better in atg5 2/2 MEFs than in wild-type MEFs. Thus the role of Atg5 in the control of wild-type L. monocytogenes replication in cultured transformed MEF cells remains controversial. Py et al. (2007) and Birmingham et al. (2007) reported that L. monocytogenes lacking LLO did not induce autophagy, as measured by LC3I lipidation and colocalization. Further, both ActA and the bacterial phospholipases (PlcA and PlcB) were reported to play a role in escaping autophagy, as measured by LC3I colocalization and bacterial growth in the presence or absence of Atg5 [23, 24] . This suggested that autophagy may play a role in the control of wild-type L. monocytogenes replication that is effectively inhibited by the action of bacterial phospholipases and/or actin polymerization. However, this hypothesis has not been directly tested in primary cells. Yano et al. (2008) showed that autophagy in Drosophila hemocytes was induced in response to L. monocytogenes infection and was dependent upon detection of peptidoglycan by the cytosolic receptor PGRP-LE as well as on bacterial expression of LLO. Lastly, Zhao et al. (2008) revealed that mice lacking Atg5 in macrophages and neutrophils had a slight increase in susceptibility to L. monocytogenes as measured by bacterial levels in spleen and liver three days after infection. However, this work did not address whether the role of Atg5 in vivo was due to autophagy or an autophagy-independent role of Atg5. Furthermore, Zhao et al. (2008) did not address whether Atg5 controls L. monocytogenes replication in primary cells.