Table 1.
Roles of Autophagy in Protection against Microbes
| Microbe | Host organism/ cell type | Autophagy genes or autophagy signals | Effects on host-pathogen interactions | References |
|---|---|---|---|---|
| VIRUSES | ||||
| RNA viruses | ||||
| Alphaviridae | ||||
| Sindbis virus | Mice (neurons) | beclin 1 | Enforced neuronal Beclin 1 expression reduces CNS viral replication, neuronal cell death, and animal mortality | Liang et al., 1998 |
| Rhabdoviridae | ||||
| Vesicular stomatitis virus | Drosophila | Atg8 Atg7 Atg12 Atg18 | Autophagy gene silencing increases viral replication in vivo and decreases fly survival | Shelly et al., 2009 |
| Tobamoviruses | ||||
| Tobacco mosaic virus (TMV) | Plants | BECLIN 1ATG3, ATG7VPS34 | Autophagy gene silencing increases TMV local replication and spread of programmed cell death in vivo | Liu et al., 2005 |
| DNA viruses | ||||
| Herpesviridae | ||||
| Herpes simplex virus 1 (HSV-1) | Mice | beclin 1 | Role for autophagy gene in protection against lethal encephalitis inferred by neuroattenuation of mutant virus that cannot inhibit Beclin 1 autophagy function | Orvedahl et al., 2007 |
| BACTERIA | ||||
| Gram-positive cocci | ||||
| Staphylococcus aureus | Mouse embryonic fibroblasts (MEFs) | Atg5 | Atg5 deletion inhibits bacterial degradation in autolysosomes, leading to delayed bacterial clearance and increased bacterial multiplication | Amano et al., 2006 |
| Group A Streptococcus | MEFs | Atg5 | Atg5 deletion inhibits bacterial degradation in autolysosomes, leading to delayed bacterial clearance and increased bacterial multiplication | Nakagawa et al., 2004 |
| Gram-positive bacilli | ||||
| Listeria monocytogenes | MEFs | Atg5 | Atg5 deletion increases replication of bacterial phospholipase mutants | Py et al., 2007 |
| Mice (macrophages) | Atg5 (macrophages) | Macrophage Atg5 required for in vivo resistance in mice | Zhao et al., 2008 | |
| Drosophila | Atg5, Atg1, peptidoglycan-recognition protein (PGRP) | Autophagy gene silencing results in failure to control L. monocytogenes replication in hemocytes in vitro or in intact fly; PGRP required to signal autophagy-mediated resistance | Yano et al., 2008 | |
| Bacillus anthracis | Mouse macrophage cell line | Autophagy induction may protect cells against anthrax lethal toxin | Tan et al., 2009 | |
| Gram-negative bacilli | ||||
| Burkholderia pseudomallei | Mouse macrophage cell lines and embryonic fibroblasts | Autophagy induction decreases intracellular bacterial survival (but no effect of Atg5 deletion in MEFs on bacterial survival) | Cullinane et al., 2008 | |
| Helicobacter pylori | Human gastric epithelial cells | Autophagy inhibition increases vacuolating toxin stability and toxin-mediated cellular vacuolation | Terebiznik et al., 2009 | |
| Human monocytic cells | Autophagy inhibition enhances and autophagy activation suppresses intracellular bacterial multiplication | Wang et al., 2009b | ||
| Pseudomonas syringae pv. tomato | Arabidopsis thaliana | ATG6 | ATG6 silencing in plants results in increased spreading programmed cell death and bacterial virulence | Patel and Dinesh-Kumar, 2008 |
| Salmonella enterica | MEFs; epithelial cells | Atg5 | Atg5 deletion results in increased intracellular bacterial growth | Birmingham et al., 2006 |
| Shigella flexneri | Dog kidney epithelial cells and MEFs | Atg5 (in MEFs) | IcsB mutant bacteria are targeted by autophagy, leading to decreased intracellular bacterial multiplication | Ogawa et al., 2005 |
| Vibrio cholerae | Human intestinal cell lines; MEFs | Atg5 (in MEFs) | Autophagy protects against toxic effects of bacterial secreted pore-forming toxin, Vibrio cholerae cytolysin | Gutierrez et al., 2007 |
| Mycobacteria | ||||
| Mycobacterium tuberculosis Bacillus Calmette-Guerin | Mouse and human primary macrophages and macrophage cell lines | Atg5 (macrophages Flox/Flox from Atg5 LysM-Cre mice) | Atg5 required for autophagic killing of mycobacteria in macrophages | Zhao et al., 2008 |
| IFNγ and immunity- related GTPases (mouse LRG-47, human IRGM), signaling through P2×7 | Autophagy induction by immune signaling, starvation, or TOR inhibition increases mycobacterial targeting to phagolysosomes and decreases mycobacterial intracellular survival | Alonso et al., 2007; Biswas et al., 2008; Gutierrez et al., 2004; Singh et al., 2006 | ||
| Th1 cytokines activate and Th2 cytokines inhibit autophagy | IL-4 and IL-13 inhibit IFNγ- or starvation-induced autophagic elimination of mycobacteria | Harris et al., 2007 | ||
| PROTOZOA | ||||
| Toxoplasma gondii | Mice (macrophages) | Atg5 | Macrophage Atg5 required for in vivo resistance in mice; mechanism believed to be autophagosome-independent recruitment of Irga6 to parasitophorous vacuole | Ling et al., 2006; Zhao et al., 2008 |