EXPERIMENTAL and MOLECULAR MEDICINE, Vol. 44, No. 2, 99-108, February 2012 Autophagy and bacterial infectious diseases Jae-Min Yuk1,2, Tamotsu Yoshimori3 and Eun-Kyeong Jo1,2,4 1Department of Microbiology and 2Infection Signaling Network Research Center Chungnam National University School of Medicine Daejeon 301-747, Korea 3Department of Genetics Graduate School of Medicine Osaka University Osaka 565-0871, Japan 4Corresponding author: Tel, 82-42-580-8243; Fax, 82-42-580-8436; E-mail, hayoungj@cnu.ac.kr http://dx.doi.org/10.3858/emm.2012.44.2.032 Accepted 30 December 2011 Available Online 19 January 2012 Abbreviations: ATG, autophagy-related protein; eis, enhanced intracellular survival; GABARAP, γ-aminobutyric acid receptor- associated protein; GAS, group A Streptococcus; Gbp, guanylate- binding protein; LC3, light chain 3; M. tuberculosis, Mycobacterium tuberculosis; NF, nuclear factor; PAMP, pathogen associated molecular pattern; ROS, reactive oxygen species reactive oxygen species; SCVs, Salmonella-containing vacuoles; SLAPs, spacious Listeria-containing phagosomes; S. Typhimurium, Salmonella enterica serovar Typhimurium; T3SSs, type three secretion systems; Th, T helper; TRAF6, tumor necrosis factor receptor-associated factor 6 Abstract Autophagy is a housekeeping process that maintains cellular homeostasis through recycling of nutrients and degradation of damaged or aged cytoplasmic constituents. Over the past several years, accumulat- ing evidence has suggested that autophagy can func- tion as an intracellular innate defense pathway in re- sponse to infection with a variety of bacteria and viruses. Autophagy plays a role as a specialized im- munologic effector and regulates innate immunity to exert antimicrobial defense mechanisms. Numerous bacterial pathogens have developed the ability to in- vade host cells or to subvert host autophagy to estab- lish a persistent infection. In this review, we have sum- marized the recent advances in our understanding of the interaction between antibacterial autophagy (xenophagy) and different bacterial pathogens. Keywords: autophagy; cytokines; immunity, Innate; infection; reactive oxygen species Introduction During macroautophagy (herein referred to as au- tophagy), cytoplasmic contents can be seques- tered in a unique double-membrane structure, the autophagosome. Through autophagy, cytoplasmic cargo in autophagosomes can be degraded by fu- sion of autophagosomes and lysosomes, and acti- vation of the lysosomal degradation pathway (Levine and Deretic, 2007). In addition to degradation of damaged organelles or materials, autophagy has received attention as a crucial component of innate defense against a variety of infectious agents. Autophagy of foreign micro-organisms, i.e., xen- ophagy, has emerged as a powerful method of eliminating intracellular bacteria (Gutierrez et al., 2004; Nakagawa et al., 2004). However, there is a complex interplay between host autophagy mecha- nisms and pathogens. Numerous microorganisms have evolved strategies to evade or subvert host autophagy to survive and establish a persistent in- fection (Campoy and Colombo, 2009b; Orvedahl and Levine, 2009). Thus, identification of mecha- nisms or virulence factors exploiting autophagy may provide a new strategy for therapeutic inter- vention in infectious diseases. Host defense against pathogens requires coor- dination of multiple innate immune signaling path- ways (Jo et al., 2007). During infection, host cells recognize the pathogen-associated molecular pat- terns of a variety of microbes through the ex- pression of various pattern recognition receptors. The recognition of foreign or danger molecules by innate receptors can trigger an intracellular signal- ing cascade, leading to activation of antimicrobial effector mechanisms to promote clearance of the infection (Jo et al., 2007; Brodsky and Medzhitov, 2009). Autophagy is considered to be one of the effector mechanisms downstream of these re- ceptors, and plays an integral role in both innate and adaptive immunity to various pathogens (Orvedahl and Levine, 2009). Autophagy also crosstalks with intracellular sig- Copyright ⓒ 2012 by the The Korean Society for Biochemistry and Molecular Biology This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.