2009; Zheng et al., 2009). Recently, it has been shown that optineurin promotes the selective au- tophagy of ubiquitin-coated cytosolic Salmonella enterica through phosphorylation of optineurin by protein kinase, TANK binding kinase 1 (Wild et al., 2011). Additionally, an ubiquitin-independent pathway mediated by a lipid second messenger, diacylgly- cerol, generated from SCV membranes, is essential for the initiation of autophagy against S. typhimurium (Shahnazari et al., 2010). Ogawa et al. (2011) re- vealed that the Atg5 binding partner Tecpr1 (tecto- nin domain-containing protein) is a cargo receptor for targeting bacterial pathogens to the selective autophagy system in Shigella-infected cells. There- fore, several autophagy receptors, which may inter- connect with other pathways or mechanisms involved in autophagy, contribute to the xenophagic elimi- nation of cytosolic bacteria in mammalian cells. The mechanisms by which autophagy receptors acti- vate host defenses against bacterial pathogens other than S. typhimurium remain to be determined. ROS, keeping a balance between antibacterial autophagy and inflammation Intracellular ROS, produced by incomplete reduction of oxygen, can oxidize and damage various macro- molecules such as proteins, lipids, and DNA, and eventually cause cell death (Azad et al., 2009; Scherz-Shouval and Elazar, 2011). Accumulating evidence points to a key role for ROS as signaling messengers, including the initiation of autophagy and various intracellular processes (Azad et al., 2009; Scherz-Shouval and Elazar, 2011). Several stimuli and stresses, including nutrient starvation, infection, and other pathological conditions, result in ROS generation (Azad et al., 2009). Cellular ROS is involved in innate immune signaling through the TLR-dependent ASK activation (Yuk et al., 2009a) and NADPH oxidase 2 pathways (Yang et al., 2009). Recently, it was revealed that ROS of mitochondrial origin are a critical factor in the antibacterial response, mediated by interaction with TRAF6 and ECSIT (evolutionarily conserved signaling intermediate in Toll pathways), which are themselves involved in the mitochondrial respiratory chain assembly (West et al., 2011). Interestingly, these are generally accepted as activating signals for autophagy in a variety of physiological and pathological settings (Azad et al., 2009; Scherz-Shouval and Elazar, 2011). Notably, TLR signaling from phagosomes can lead to initiation of antibacterial autophagy through generation of NAPDH oxidase NOX2-dependent ROS (Huang and Brumell, 2009). Excessive ROS of cellular and Autophagy in infectious diseases 105 mitochondrial origin is associated with activation of proinflammatory responses, autophagy, and cell death in macrophages infected with enhanced intracellular survival (eis)-deficient mycobacteria (Shin et al., 2010a). In contrast, recent evidence suggests that auto- phagy is also essential for prevention of excessive inflammation. Depletion of the autophagy proteins LC3B and beclin 1 significantly enhances NLRP3- dependent inflammasome activation and IL-1β and IL-18 levels, and increases susceptibility to LPS- induced septic shock in vivo (Nakahira et al., 2011). Intriguingly, in this case, mitochondrial ROS are also thought to be important for mediating inflam- matory responses, even in the autophagy-deficient host (Nakahira et al., 2011). This effect was dependent on the release of mitochondrial DNA into the cytosol and increased mitochondrial ROS generation (Nakahira et al., 2011). Thus, it seems that coordinated interplay between autophagy acti- vation and ROS-dependent signaling is necessary for the homeostatic regulation of innate defense and inflammation. Concluding remarks Since the roles of autophagy have been revealed in host immune responses, a number of recent in vitro, in vivo, and molecular studies have provided evidence of selective autophagic degradation of bacteria and viruses (xenophagy). Moreover, rapid advances have been made in elucidating the mechanisms underlying the cell’s defensive response to intracellular bacteria. In this review we have emphasized that numerous bacterial pathogens possess multiple strategies for avoiding or circum- venting host defense pathways to ensure their survival and replication within the host. Thus, it is not surprising that autophagy pathways cross talk with innate immunity to contribute to the combat of invading pathogens. Various immune effectors have been identified as cooperating with and regulating the autophagic responses against invading bacterial infection, although additional host factors and detailed mechanisms remain to be delineated. Here, we propose that the host autophagy system has evolved strategies to manipulate certain autophagic adaptors or cargo receptors to promote autophagy targeting to bacteria, proteins, and damaged organelles. Several important questions related to the extended and distinct roles of immune effectors or cargo receptors, i.e., whether they are involved in defense against specific pathogens or general microbial invaders, should be answered in future studies. Current and future revelations regarding