100 Exp. Mol. Med. Vol. 44(2), 99-108, 2012 naling molecules and effectors (Brodsky and Medzhitov, 2009; Shahnazari and Brumell, 2011). Through these interactions, autophagy carries out not only direct microbial degradation but also other protective mechanisms, such as lysozyme secretion, the ubiquitin-mediated pathway, and antigen pre- sentation (Brodsky and Medzhitov, 2009; Shahnazari and Brumell, 2011). In particular, the autophagic or cargo receptors have received much attention, since they play an important role in transporting ubiquitinated microbial cargos to the autophagy machinery (Pankiv et al., 2007; Ichimura et al., 2008; Kirkin et al., 2009b; Thurston et al., 2009; von Muhlinen et al., 2010). Recent studies have provided evidence that autophagy acts as a ‘tuning module’ in the regulation of innate immunity to prevent excessive inflam - matory responses and inflammasome signaling (Sumpter and Levine, 2010). Generation of reactive oxygen species (ROS) of cellular and mitochondrial origin is thought to play an important role in auto- phagy regulation, thus influencing innate defense (Azad et al., 2009; Scherz-Shouval and Elazar, 2011). The specific role and regulatory mechanisms of autophagy in connection with innate immune pathways during infection will be discussed here. Additionally, the molecular mechanisms by which multiple bacteria and viruses evade and/or resist autophagy will be covered in this review. Xenophagy: autophagic control of intracellular bacterial pathogens Autophagy is a mechanism for adjusting cellular quality and quantity through capture and degradation of portions of the cytosol or organelles in response to diverse stress or stimuli, including infection (Deretic and Levine, 2009). Autophagy is a means of bulk degradation of cytoplasmic components within lysosomes. During this process, cytoplasmic constituents are delivered to lysosomes for degra- dation (Mizushima and Levine, 2008). Although au- tophagy is fundamentally a ‘self-eating’ process, it also facilitates degradation of pathogens as a ‘xenophagy’ process (Huang and Brumell, 2009). Accumulating evidence indicates that autophagy acts as a defense mechanism against multiple invading microbes (Deretic and Levine, 2009). During infection, host autophagic responses can target several steps of bacterial invasion. For example, autophagy can target bacteria within vacuolar mem- branous compartments. Intracellular pathogens, such as Mycobacterium tuberculosis (M. tuberculosis), can actively survive within host cells and exploit host defense by inhibition of phagosomal maturation (Gutierrez et al., 2004; Yuk et al., 2009b). Auto- phagy activation by nutrient starvation or rapamycin treatment leads to co-localization of mycobacterial phagosomes with autophagosomes to overcome the inhibition of phagosomal maturation by myco- bacteria, thereby resulting in suppression of intra- cellular bacterial survival (Gutierrez et al., 2004; Yuk et al., 2009b). Stimulation of host autophagy by treatment with vitamin D significantly enhanced the antimicrobial responses against M. tuberculosis in human macrophages. This effect was mediated by cathelicidin, a peptide that is induced by vitamin D and promotes co-localization of bacterial pha- gosomes and autophagosomes (Yuk et al., 2009b). These data suggest that autophagy contributes to elimination of bacteria by overcoming bacterial resistance to lysosomal access. Another example is group A Streptococcus (GAS). When GAS enters epithelial cells via endocytosis, they can escape from the endosomes to the cytoplasm by secretion of streptolysin O, a pore- forming toxin (Nakagawa et al., 2004). GAS is then trapped in autophagosome-like compartments, which mature into autolysosomes and so eliminate the bacteria (Nakagawa et al., 2004). Mechanistically, the host small G proteins, Rab5 and Rab7, are associated with autophagosome formation and the progression of endosome maturation in cells infected with GAS (Sakurai et al., 2010). Two endocytic soluble N-ethylmaleimide-sensitive factor attachment protein receptors, VAMP8 from lysosomes and Vti1b from autophagic compartments, are required for the successful fusion of GAS-containing xenophagosomes with lysosomes, which facilitates xenophagy (Furuta et al., 2010). The third mode of anti-bacterial action of au- tophagy is receptor-mediated recruitment of bac- teria to autophagosomes. Some populations of Salmonella enterica serovar Typhimurium (S. Typhimurium) are known to invade mammalian cells and replicate in Salmonella-containing va- cuoles (SCVs). During this process, two kinds of Salmonella pathogenicity island (SPI) encoding type III secretion systems (T3SSs) are involved: the SPI-2 encoded T3SS facilitates bacterial growth, whereas the SPI-1 encoded T3SS causes damage to SCV (Birmingham et al., 2006), which activates the autophagic process. The autophagy system targets the intracellular bacteria present within damaged SCVs, and contributes to restriction of bacterial growth during infection (Birmingham et al., 2006). The autophagy receptor p62/SQSTM1, an adaptor protein for degradation of cargo tagged with ubiquitinated protein, is recruited to autoph- agy-targeted S. Typhimurium and required for the