Immunology and Cell Biology (2015) 93, 1–2 & 2015 Australasian Society for Immunology Inc. All rights reserved 0818-9641/15 www.nature.com/icb
EDITORIAL
Autophagy and immunity Immunology and Cell Biology (2015) 93, 1–2; doi:10.1038/icb.2014.98
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utophagy is everywhere. It is a constitutive process in most eukaryotic cells. It is involved in a multitude of cellular processes, implicated in numerous diseases and seems to be making its way into almost every biological laboratory across the globe. For those of us who have worked on autophagy for a while, this is both exciting and worrying (competition is not always comforting). For the researcher looking at autophagy for the first time, this might be incredibly daunting. A search for ‘autophagy’ on Pubmed brings up 17300 articles (with this number probably increased significantly by the time this you are reading this). A search for ‘autophagy and immunity’ brings up 1355 articles, ‘autophagy and cytokines’ 877 and ‘autophagy and pathogen’ 582 articles. Even ‘autophagy and chicken’ brings up 35 articles. Autophagy has come a long way since its discovery in the 1960s. Autophagy is a growth business. Taken from the Greek, ‘auto’ (self) ‘phagy’ (eating) is, at its core, a way of targeting intracellular components (proteins, organelles and intracellular pathogens) for degradation by lysosomes (or vacuoles in yeast). Of course, autophagy is not a single process. There is chaperone-mediated autophagy, microautophagy, macroautophagy and LC3-associated phagocytosis (LAP) (not strictly autophagy, but related). And the nomenclature is growing. There is autophagic targeting and degradation of mitochondria (mitophagy), peroxisomes (pexophagy), endoplasmic reticulum (reticulophagy), ribosomes (ribophagy), ubiquitinated protein aggregates (aggrephagy) and pathogens (xenophagy). Moreover, recent studies have demonstrated roles for autophagy in antigen presentation, secretory pathways and the selective targeting of inflammasome components and the pro-inflammatory cytokine IL-1β (inflammophagy and cytokinophagy, anyone?). Who knows what else autophagy might do? This is why it is such an interesting topic. In this Special Feature of Immunology and Cell Biology, we focus on the many roles of autophagy in the immune system, an area of research very close to our hearts and one that is growing at a frightening and exciting rate. In many ways, this Special Feature was born from a meeting held in Melbourne in February 2014. ‘Ozophagy 2014’ (a satellite meeting of the 39th Lorne Conference on Protein Structure and Function Conference) was the first meeting of its type to bring together autophagy researchers in Australia. As a result, we have invited articles from a selection of Australian and international researchers that cover a range of topics in this rapidly expanding field. As Michael Lazarou explains, mitophagy is central to many immune cell functions and represents a critical intersection between autophagy and the immune system.1 Important studies
have demonstrated a role for autophagy in controlling the release of mitochondrial DNA and reactive oxygen species (ROS), which would otherwise activate inflammasome assembly and the release of pro-inflammatory cytokines, including IL-1β and IL-18. Dinkins et al.2 further discuss this topic, in the context of the various roles of autophagy in the host immune response to HIV infection.2 The role of autophagy and LAP in the immune response to Burkholderia spp. is the subject of the review by Devenish and Lai.3 B. pseudomallei is the causative agent of melioidosis, a serious infectious disease native to South East Asia and Northern Australia. The many newly appreciated roles for autophagy in T cell biology, from development to differentiation to activation to homeostasis, are the focus of the article by Bronietzki et al.4 However, while autophagy is an important cellular homeostatic mechanism and promotes cell survival during amino acid starvation, there are many cases where it may instead facilitate cell death. In this Special Feature, Denton et al.5 discuss the involvement of autophagy in specific cell death pathways and how this may impact on immune responses. Finally, Leveque et al.6 discuss the potentially critical roles of autophagy in haematopoietic stem-cell (HSC) transplantation, both in promoting HSC survival and function and regulating the inflammatory response at the time of engraftment. Together, these articles highlight some of the hot topics in the field of autophagy and immunity that will hopefully serve as a catalyst for further studies. It is abundantly clear that autophagy has vital roles to play in the maintenance, survival, death and functions of immune cells that impact on our ability to respond to infection, inflammation and autoimmunity. Thus, by better understanding how autophagy regulates immune responses, we may be able to develop novel targeted therapies to modulate autophagy (in some cases inhibit, in others induce). Our appreciation of autophagy has come a long way in 50 years, but as interest continues to gather pace and new reagents and techniques are developed, things can only get bigger and better. And hopefully there will be more studies in chickens. Justine D Mintern1 and James Harris2 Department of Biochemistry and Molecular Biology, The University of Melbourne, Bio21 Molecular Science and Biotechnology Institute, Parkville, Victoria, Australia and 2Centre for Inflammatory Diseases, School of Clinical Sciences at Monash, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia E-mail:
[email protected] 1
Editorial 2
1 Lazarou M. Keeping the immune system in check: a role for mitophagy. Immunol Cell Biol 2015; 93: 3–10. 2 Dinkins C, Pilli M, Kehrl JH. Roles of autophagy in HIV infection. Immunol Cell Biol 2015; 93: 11–17. 3 Devenish RJ, Lai S-c. Autophagy and Burkholderia. Immunol Cell Biol 2015; 93: 18–24.
Immunology and Cell Biology
4 Bronietzki AW, Schuster M, Schmitz I. Autophagy in T-cell development, activation and differentiation. Immunol Cell Biol 2015; 93: 25–34. 5 Denton D, Xu T, Kumar S. Autophagy as a pro-death pathway. Immunol Cell Biol 2015; 93: 35–42. 6 Leveque L, Le Texia L, Lineburg KE, Hill GR, MacDonald KPA. Autophagy and haematopoietic stem cell transplantation. Immunol Cell Biol 2015; 93: 43–50.
