EDITORIAL

Autophagy and immunity

Immunology and Cell Biology (2015) 93, 1–2; doi:10.1038/icb.2014.98

Autophagy is everywhere. It is a constitutive process inmost eukaryotic cells. It is involved in a multitude of cellular

processes, implicated in numerous diseases and seems to bemaking its way into almost every biological laboratory across theglobe. For those of us who have worked on autophagy for awhile, this is both exciting and worrying (competition is not alwayscomforting). For the researcher looking at autophagy for the first time,this might be incredibly daunting. A search for ‘autophagy’ onPubmed brings up 17300 articles (with this number probablyincreased significantly by the time this you are reading this). A searchfor ‘autophagy and immunity’ brings up 1355 articles, ‘autophagy andcytokines’ 877 and ‘autophagy and pathogen’ 582 articles. Even‘autophagy and chicken’ brings up 35 articles. Autophagy has comea long way since its discovery in the 1960s. Autophagy is a growthbusiness.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 singleprocess. There is chaperone-mediated autophagy, microauto-phagy, macroautophagy and LC3-associated phagocytosis (LAP)(not strictly autophagy, but related). And the nomenclature isgrowing. There is autophagic targeting and degradation of mito-chondria (mitophagy), peroxisomes (pexophagy), endoplasmicreticulum (reticulophagy), ribosomes (ribophagy), ubiquitinatedprotein aggregates (aggrephagy) and pathogens (xenophagy).Moreover, recent studies have demonstrated roles for autophagyin antigen presentation, secretory pathways and the selective targetingof inflammasome components and the pro-inflammatory cytokineIL-1β (inflammophagy and cytokinophagy, anyone?). Who knowswhat else autophagy might do? This is why it is such aninteresting topic.In this Special Feature of Immunology and Cell Biology, we focus on

the many roles of autophagy in the immune system, an area ofresearch very close to our hearts and one that is growing at afrightening and exciting rate. In many ways, this Special Feature wasborn from a meeting held in Melbourne in February 2014. ‘Ozophagy2014’ (a satellite meeting of the 39th Lorne Conference on ProteinStructure and Function Conference) was the first meeting of itstype to bring together autophagy researchers in Australia. As a result,we have invited articles from a selection of Australian and interna-tional researchers that cover a range of topics in this rapidlyexpanding field.As Michael Lazarou explains, mitophagy is central to many

immune cell functions and represents a critical intersectionbetween autophagy and the immune system.1 Important studies

have demonstrated a role for autophagy in controlling therelease of mitochondrial DNA and reactive oxygen species (ROS),which would otherwise activate inflammasome assembly and therelease of pro-inflammatory cytokines, including IL-1β andIL-18. Dinkins et al.2 further discuss this topic, in the contextof the various roles of autophagy in the host immune responseto HIV infection.2 The role of autophagy and LAP in theimmune response to Burkholderia spp. is the subject of the reviewby Devenish and Lai.3 B. pseudomallei is the causative agent ofmelioidosis, a serious infectious disease native to South East Asiaand Northern Australia.The many newly appreciated roles for autophagy in T cell

biology, from development to differentiation to activation tohomeostasis, are the focus of the article by Bronietzki et al.4

However, while autophagy is an important cellular homeostaticmechanism 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 involvementof autophagy in specific cell death pathways and how this mayimpact on immune responses. Finally, Leveque et al.6

discuss the potentially critical roles of autophagy in haematopoieticstem-cell (HSC) transplantation, both in promoting HSC survival andfunction and regulating the inflammatory response at the time ofengraftment.Together, these articles highlight some of the hot topics in the

field of autophagy and immunity that will hopefully serve as acatalyst for further studies. It is abundantly clear that autophagyhas vital roles to play in the maintenance, survival, death and functionsof immune cells that impact on our ability to respond to infection,inflammation and autoimmunity. Thus, by better understandinghow autophagy regulates immune responses, we may be able todevelop novel targeted therapies to modulate autophagy (in some casesinhibit, in others induce). Our appreciation of autophagy has come along way in 50 years, but as interest continues to gather pace and newreagents and techniques are developed, things can only get biggerand better.And hopefully there will be more studies in chickens.

Justine D Mintern1 and James Harris21Department of Biochemistry and Molecular Biology, The University

of Melbourne, Bio21 Molecular Science and BiotechnologyInstitute, Parkville, Victoria, Australia and 2Centre for InflammatoryDiseases, School of Clinical Sciences at Monash, Faculty of Medicine,

Nursing and Health Sciences, Monash University, Clayton,Victoria, Australia

E-mail: jim.harris@monash.edu

Immunology and Cell Biology (2015) 93, 1–2& 2015 Australasian Society for Immunology Inc. All rights reserved 0818-9641/15www.nature.com/icb

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 Biol2015; 93: 11–17.

3 Devenish RJ, Lai S-c. Autophagy and Burkholderia. Immunol Cell Biol 2015; 93:18–24.

4 Bronietzki AW, Schuster M, Schmitz I. Autophagy in T-cell development, activation anddifferentiation. 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.

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Immunology and Cell Biology