BookID 160045_ChapID FM_Proof# 1 - 17/4/2009

Current Topics in and

Volume 335

Series Editors R. John Collier Department of Microbiology and Molecular , Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA Richard W. Compans Emory University School of Medicine, Department of Microbiology and Immunology, 3001 Rollins Research Center, Atlanta, GA 30322, USA Max D. Cooper Department of Pathology and Laboratory Medicine, Georgia Research Alliance, Emory University, 1462 Clifton Road, Atlanta, GA 30322, USA Yuri Y. Gleba ICON Genetics AG, Biozentrum Halle, Weinbergweg 22, Halle 6120, Germany Tasuku Honjo Department of Medical Chemistry, Kyoto University, Faculty of Medicine, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan Hilary Koprowski Thomas Jefferson University, Department of Cancer Biology, Biotechnology Foundation Laboratories, 1020 Locust Street, Suite M85 JAH, Philadelphia, PA 19107-6799, USA Bernard Malissen Centre d’Immunologie de Marseille-Luminy, Parc Scientifique de Luminy, Case 906, Marseille Cedex 9 13288, France Fritz Melchers Biozentrum, Department of Cell Biology, University of Basel, Klingelbergstr. 50–70, 4056 Basel Switzerland Michael B.A. Oldstone Department of Neuropharmacology, Division of , The Scripps Research Institute, 10550 N. Torrey Pines, La Jolla, CA 92037, USA Sjur Olsnes Department of , Institute for Cancer Research, The Norwegian Radium Hospital, Montebello 0310 Oslo, Norway Herbert W. “Skip” Virgin Washington University School of Medicine, Pathology and Immunology, University Box 8118, 660 South Euclid Avenue, Saint Louis, Missouri 63110, USA Peter K. Vogt The Scripps Research Institute, Dept. of Molecular & Exp. Medicine, Division of Oncovirology, 10550 N. Torrey Pines. BCC-239, La Jolla, CA 92037, USA BookID 160045_ChapID FM_Proof# 1 - 17/4/2009 BookID 160045_ChapID FM_Proof# 1 - 17/4/2009

ii

Current Topics in Microbiology and Immunology

Previously published volumes Further volumes can be found at springer.com

Vol. 310: Doerfler, Walter; Böhm, Petra (Eds.): Vol. 322: Romeo, Tony (Ed.): DNA Methylation: Development, Bacterial Biofilms. 2008. XII, 299. Genetic Disease and Cancer. 2006. 25 figs. ISBN 978-3-540-75417-6 X, 284 pp. ISBN 3-540-31180-7 Vol. 323: Tracy, Steven; Oberste, M. Steven; Vol. 311: Pulendran, Bali; Ahmed, Rafi (Eds.): Drescher, Kristen M. (Eds.): From Innate Immunity to Immunological Group B Coxsackieviruses. 2008. Memory. 2006. 13 figs. X, 177 pp. ISBN 978-3-540-75545-6 ISBN 3-540-32635-9 Vol. 324: Nomura, Tatsuji; Watanabe, Vol. 312: Boshoff, Chris; Weiss, Robin A. (Eds.): Takeshi; Habu, Sonoko (Eds.): Kaposi Sarcoma Herpesvirus: Humanized Mice. 2008. New Perspectives. 2006. 29 figs. XVI, 330 pp. ISBN 978-3-540-75646-0 ISBN 3-540-34343-1 Vol. 325: Shenk, Thomas E.; Stinski, Vol. 313: Pandolfi, Pier P.; Vogt, Peter K.(Eds.): Mark F. (Eds.): Acute Promyelocytic Leukemia. 2007. Human Cytomegalovirus. 2008. 16 figs. VIII, 273 pp. ISBN 3-540-34592-2 ISBN 978-3-540-77348-1 Vol. 314: Moody, Branch D. (Ed.): Vol. 326: Reddy, Anireddy S.N; Golovkin, T Cell Activation by CD1 and Lipid Antigens, Maxim (Eds.): 2007, 25 figs. VIII, 348 pp. Nuclear pre-mRNA processing in plants. 2008. ISBN 978-3-540-69510-3 ISBN 978-3-540-76775-6 Vol. 315: Childs, James, E.; Mackenzie, John S.; Vol. 327: Manchester, Marianne; Richt, Jürgen A. (Eds.): Steinmetz, Nicole F. (Eds.): Wildlife and Emerging Zoonotic Diseases: Viruses and Nanotechnology. 2008. The Biology, Circumstances and Consequences of ISBN 978-3-540-69376-5 Cross-Species Transmission. 2007. 49 figs. VII, 524 pp. ISBN 978-3-540-70961-9 Vol. 328: van Etten, (Ed.): Lesser Known Large dsDNA Viruses. 2008. Vol. 316: Pitha, Paula M. (Ed.): ISBN 978-3-540-68617-0 Interferon: The 50th Anniversary. 2007. VII, 391 pp. ISBN 978-3-540-71328-9 Vol. 329: Diane E. Griffin; Michael B.A. Oldstone (Eds.): Measles 2009. Vol. 317: Dessain, Scott K. (Ed.): ISBN 978-3-540-70522-2 Human Antibody Therapeutics for Viral Disease. 2007. XI, 202 pp. ISBN 978-3-540-72144-4 Vol. 330: Diane E. Griffin; Michael B.A. Oldstone (Eds.): Measles 2009. Vol. 318: Rodriguez, Moses (Ed.): ISBN 978-3-540-70616-8 Advances in Multiple Sclerosis and Experimental Demyelinating Diseases. 2008. Vol. 331 Villiers, E. M. de (Eds.): XIV, 376 pp. ISBN 978-3-540-73679-9 TT Viruses. 2009. ISBN 978-3-540-70917-8 Vol. 319: Manser, Tim (Ed.): Specialization and Complementation Vol. 332 Karasev A.(Ed.): of Humoral Immune Responses to Infection. Plant produced Microbial Vaccines. 2009. 2008. XII, 174 pp. ISBN 978-3-540-73899-2 ISBN 978-3-540- 70857-5 Vol. 320: Paddison, Patrick J.; Vol. 333 Richard W. Compans; Vogt, Peter K.(Eds.): RNA Interference. 2008. Walter A. Orenstein (Eds.): VIII, 273 pp. ISBN 978-3-540-75156-4 Vaccines for Pandemic Influenza. 2009. ISBN 978-3-540-92164-6 Vol. 321: Beutler, Bruce (Ed.): Immunology, Phenotype First: How Mutations Vol. 334 Dorian McGavern; Have Established New Principles and Michael Dustin (Eds.): Pathways in Immunology. 2008. XIV, 221 pp. Visualizing Immunity. 2009. ISBN 978-3-540-75202-8 ISBN 978-3-540-93862-0 BookID 160045_ChapID FM_Proof# 1 - 17/4/2009

Beth Levine ● Tamotsu Yoshimori ● Vojo Deretic Editors

Autophagy in Infection and Immunity BookID 160045_ChapID FM_Proof# 1 - 17/4/2009 BookID 160045_ChapID FM_Proof# 1 - 17/4/2009

Editors Beth Levine Tamotsu Yoshimori Howard Hughes Medical Institute Department of Cell Regulation Department of Internal Medicine Research Insitute for Microbial Diseases and Microbiology Osaka University University of Texas 3-1, Yamadaoka, Suita, Osaka 565-0871 Southwestern Medical Center Japan 5323 Harry Hines Blvd. [email protected] Dallas TX 75390-9113, USA [email protected]

Vojo Deretic Department of Molecular Genetics and Microbiology Health Sciences Center University of New Mexico 915 Camino de Salud NE., Albuquerque NM 87131 USA [email protected]

ISBN 978-3-642-00301-1 e-ISBN 978-3-642-00302-8 DOI 10.1007/978-3-642-00302-8 Springer Dordrecht Heidelberg London New York

Current Topics in Microbiology and Immunology ISSN 0070-217x

Library of Congress Catalog Number: 2009926065

© Springer-Verlag Berlin Heidelberg 2009 This work is subject to copyright. All rights reserved, whether the whole or part of the ­material is ­concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September, 9, 1965, in its current version, and permission for use must always be obtained from Springer-Verlag. Violations are liable for prosecution under the German Copyright Law. The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protec- tive laws and regulations and therefore free for general use. Product liability: The publisher cannot guarantee the accuracy of any information about dosage and ­application contained in this book. In every individual case the user must check such information by ­consulting the relevant literature.

Cover legend : The cover image illustrates different stages of the autophagic degradation of bacteria, including an isolation membrane surrounding bacteria, an autophagosome containing intact bacteria, and an autolyososome containing partially degraded bacteria. The discovery of autophagic degradation of bacteria was a seminal observation that opened up the field of autophagy in infection and immunity.

Cover illustration by Angela Diehl and Anthony Orvedahl, University of Texas Southwestern Medical Center, Dallas, Texas, USA

Cover design: WMX Design Gmbh, Heidelberg

Printed on acid-free paper

Springer is part of Springer Science+Business Media (www.springer.com) BookID 160045_ChapID FM_Proof# 1 - 17/4/2009

Preface

Autophagy is a fundamental biological process that enables cells to adjust ­cytoplasmic mass, quality and organization through capture and autodigestion of their cytoplasmic components. Autophagic targets range in size and complexity from individual long-lived macromolecules to whole organelles and microbial invaders. The principal role of this ubiquitous eukaryotic homeostatic mechanism is to ensure cell survival under adverse conditions, including nutrient absence, growth factor withdrawal, accumulation of toxic protein aggregates, and faulty organelles (e.g., leaky mitochondria), or infection by intracellular pathogens. The physiologic and pathophysiologic roles of autophagy (and defects in autophagy) are vast, encompassing cancer, neurodegeneration, metabolic diseases, aging, and (as of more recently) immunity. The immunological roles of autophagy fall into two broad categories, including: (1) effects on the control of general homeostasis in immune cells that parallel its roles in other cell types in the body, and; (2) effects on specialized functions of immune cells or other cellular targets of infection that enable the host to effectively deal with microbes or microbial products. In this volume, experts in autophagy provide overviews and more detailed dissections of the basic molecular and cellular mechanisms of autophagy (chapter by Yang and Klionsky), the signaling cascades that control these processes (chapter by Codogno and colleagues), and the fundamental and applied physiological roles of autophagy (chapter by Mizushima). The role of autophagy in cellular homeostasis as it relates to immunity is covered in two chapters; Pua and He describe the role of autophagy in lymphocyte homeostasis and Espert and Biard-Piechaczyk describe the effects of HIV on lymphocyte cell death through autophagy. These chapters provide contrasting examples of how autophagy can be used to normally adjust lymphocyte populations or be misdirected by a potent virus to deplete certain types of immune cells. A similar theme of “pros and co s” is seen in the chapters that comprise the bulk of this volume, covering what is likely to be the most ancient specialized immune function of autophagy: the direct elimination of intracellular microbes. In the chapters by Orvedahl and Levine, Deretic and colleagues, Huang and Brumell, Yoshimori and Amano, and Sabauste, autophagy is revealed in its primordial immune form of an innate, cell-autonomous defense against the microbes that manage to erode into or specifically invade the interior of the eukaryotic cell. The chapters by Kirkegaard, Orvedahl and Levine, and Campoy and Colombo

v BookID 160045_ChapID FM_Proof# 1 - 17/4/2009 BookID 160045_ChapID FM_Proof# 1 - 17/4/2009

vi Preface reveal the flip side of these relationships, addressing specialized adaptations that successful intracellular pathogens have evolved to deal with autophagy as an anti­ microbial mechanism. Moreover, the broad role of autophagy as a cell-autonomous innate immunity mechanism that is deeply engrained in the eukaryotic cell is evidenced by its role in plants, as discussed in the chapter by Dinesh-Kumar and colleagues. Lastly, the chapters by Tal and Iwasaki, Gannagé and Münz, and Virgin and colleagues cover some of the most intriguing immunological applications of autophagy, including: (1) the ability of autophagosomes to capture cytosolic microbial products for presentation to the lumenally-oriented innate immunity receptors such as Toll-like receptors (Tal and Iwasaki), thus activating innate immunity; (2) a similar topological inversion function of autophagy in antigen presentation, whereby microbial antigens expressed in the cytosol of the host cell can be processed and loaded onto lumen-facing MHC II molecules for proper presentation to T cells (Gannagé and Münz), thereby functioning in adaptive immunity as well as in thymic T-cell selection; and (3) the role of autophagy genes as their function relates to specialized aspects of highly differentiated cells in the context of understanding inflammatory disorders such as Crohn’s disease (Virgin and colleagues). The chapters in the book describe an increasingly complex set of interactions that are beginning to be unraveled between the autophagy pathway, infectious dis- eases, and immunity. In its most primal form, autophagy may be a universal defense mechanism by which individual eukaryotic cells (or unicellular organisms) protect themselves in a cell-autonomous fashion by “eating” the microbes that attack them. With the evolution of metazoan organisms, the autophagy pathway has likely been utilized to enable such organisms to develop a more complex immune system. Not only is autophagy a primordial defense mechanism, it is also a pathway that shapes the dynamics of immune cell populations, that contributes to immunological toler- ance and the control of inflammation, and that links pathogen recognition to the activation of innate and adaptive immunity. And—based upon the pace of new discoveries in this area—this list may just be the tip of the iceberg. Hopefully, this volume of Current Topics in Microbiology and Immunology will stimulate investi- gators to delve even deeper into this exciting field. Dallas, TX, USA Beth Levine Osaka, Japan Tamotsu Yoshimori Albuquerque, NM, USA Vojo Deretic BookID 160045_ChapID FM_Proof# 1 - 17/4/2009

Contents

An Overview of the Molecular Mechanism of Autophagy...... 1 Zhifen Yang and Daniel J. Klionsky

Macroautophagy Signaling and Regulation...... 33 Audrey Esclatine, Magali Chaumorcel, and Patrice Codogno

Physiological Functions of Autophagy...... 71 Noboru Mizushima

Autophagy and Lymphocyte Homeostasis...... 85 Heather H. Pua and You-Wen He

Autophagy and Innate Recognition Systems...... 107 Michal Caspi Tal and Akiko Iwasaki

Autophagy in MHC Class II Presentation of Endogenous Antigens...... 123 Monique Gannagé and Christian Münz

Role of Autophagy and Autophagy Genes in Inflammatory Bowel Disease...... 141 Ken Cadwell, Thaddeus S. Stappenbeck, and Herbert W. Virgin

Autophagy in Immunity Against Mycobacterium tuberculosis: a Model System to Dissect Immunological Roles of Autophagy...... 169 Vojo Deretic, Monica Delgado, Isabelle Vergne, Sharon Master, Sergio De Haro, Marisa Ponpuak, and Sudha Singh

Autophagy in Immunity Against Intracellular Bacteria...... 189 Ju Huang and John H. Brumell

Group A Streptococcus: A Loser in the Battle with Autophagy...... 217 Tamotsu Yoshimori and Atsuo Amano

vii BookID 160045_ChapID FM_Proof# 1 - 17/4/2009 BookID 160045_ChapID FM_Proof# 1 - 17/4/2009

viii Contents

Autophagy Subversion by Bacteria...... 227 Emanuel Campoy and María I. Colombo

Autophagy in Immunity Against Toxoplasma gondii...... 251 Carlos S. Subauste

Autophagy in Mammalian Antiviral Immunity...... 267 Anthony Orvedahl and Beth Levine

Something Old, Something New: Plant Innate Immunity and Autophagy...... 287 Montrell Seay, Andrew P. Hayward, Jeffrey Tsao, and S.P. Dinesh-Kumar

Autophagy in HIV-Induced T Cell Death...... 307 Lucile Espert and Martine Biard-Piechaczyk

Subversion of the Cellular Autophagy Pathway by Viruses...... 323 Karla Kirkegaard

Index...... 335 BookID 160045_ChapID FM_Proof# 1 - 17/4/2009

Contributors

Atsuo Amano Department of Oral Frontier Biology, Osaka University Graduate School of Dentistry, Suita-Osaka 565-0871, Japan Martine Biard-Piechaczyk CPBS, CNRS UMR5236/University of Montpellier, Institut de Biologie, 4, Bd Henri IV, CS 69033, 34965 Montpellier Cedex 2, France [email protected] John H. Brumell Cell Biology Program, Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada; Department of Molecular Genetics and Institute of Medical Science, University of Toronto, Toronto, ON, Canada M5S 1A8 [email protected] Ken Cadwell Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA Emanuel Campoy Laboratorio de Biología Celular y Molecular, Instituto de Histología y Embriología (IHEM)-CONICET, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina Magali Chaumorcel INSERM U756 Faculté de Pharmacie, 5 rue Jean-Baptiste Clément 92290 Châtenay-Malabry, France; Université Paris-Sud 11, Faculté de Pharmacie, 5 rue Jean-Baptiste Clément 92290 Châtenay-Malabry, France

ix BookID 160045_ChapID FM_Proof# 1 - 17/4/2009 BookID 160045_ChapID FM_Proof# 1 - 17/4/2009

x Contributors

Patrice Codogno INSERM U756 Faculté de Pharmacie, 5 rue Jean-Baptiste Clément 92290 Châtenay-Malabry, France Université Paris-Sud 11, Faculté de Pharmacie, 5 rue Jean-Baptiste Clément 92290 Châtenay-Malabry, France [email protected] María I. Colombo Laboratorio de Biología Celular y Molecular, Instituto de Histología y Embriología (IHEM)-CONICET, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Casilla de Correo 56, Centro Universitario, Parque General San Martín, (5500) Mendoza, Argentina [email protected] Sergio De Haro Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud NE, Albuquerque, NM 87131, USA Monica Delgado Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud NE, Albuquerque, NM 87131, USA Vojo Deretic Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, NE, Albuquerque, NM 87131, USA [email protected] S.P. Dinesh-Kumar Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520-8103, USA [email protected] Audrey Esclatine INSERM U756 Faculté de Pharmacie, 5 rue Jean-Baptiste Clément 92290 Châtenay-Malabry, France; Université Paris-Sud 11, Faculté de Pharmacie, 5 rue Jean-Baptiste Clément 92290 Châtenay-Malabry, France Lucile Espert CPBS, CNRS UMR5236/University of Montpellier, Institut de Biologie, 4, Bd Henri IV, CS 69033, 34965 Montpellier Cedex 2, France [email protected] BookID 160045_ChapID FM_Proof# 1 - 17/4/2009

Contributors xi

Monique Gannagé Viral Immunobiology, Institute of Experimental Immunology, University Hospital of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland Andrew Hayward Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520-8103, USA You-Wen He Box 3010, Department of Immunology, DUMC, Durham, NC 27710, USA [email protected] Ju Huang Cell Biology Program, Hospital for Sick Children, Toronto, ON, Canada M5G 1X8 Akiko Iwasaki Department of Immunobiology, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06520, USA [email protected] Karla Kirkegaard Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford CA 94305, USA [email protected] Daniel J. Klionsky Life Sciences Institute and Departments of Molecular, Cellular and Developmental Biology and Biological Chemistry, University of Michigan, Ann Arbor, MI 48109-2216, USA [email protected] Beth Levine Howard Hughes Medical Institute, Departments of Internal Medicine and Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA [email protected] Sharon Master Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud NE, Albuquerque, NM 87131, USA BookID 160045_ChapID FM_Proof# 1 - 17/4/2009 BookID 160045_ChapID FM_Proof# 1 - 17/4/2009

xii Contributors

Noboru Mizushima Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113-8519, Japan [email protected] Christian Münz Viral Immunobiology, Institute of Experimental Immunology, University Hospital of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland [email protected] Anthony Orvedahl Departments of Internal Medicine and Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA Marisa Ponpuak Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud NE, Albuquerque, NM 87131, USA Heather H. Pua Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA Montrell Seay Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520-8103, USA Sudha Singh Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud NE, Albuquerque, NM 87131, USA Thaddeus S. Stappenbeck Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA Carlos S. Subauste Department of Ophthalmology and Visual Sciences, and Division of Infectious Diseases and HIV Medicine, Department of Medicine, Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA [email protected] BookID 160045_ChapID FM_Proof# 1 - 17/4/2009

Contributors xiii

Michal Caspi Tal Department of Immunobiology, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06520, USA Jeffrey Tsao Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520-8103, USA Isabelle Vergne Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud NE, Albuquerque, NM 87131, USA Herbert W. Virgin Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA [email protected] Zhifen Yang Life Sciences Institute and Departments of Molecular, Cellular and Developmental Biology and Biological Chemistry, University of Michigan, Ann Arbor, MI 48109-2216, USA Tamotsu Yoshimori Department of Cell Regulation, Research Institute for Microbial Diseases, Osaka University, Suita-Osaka 565-0871, Japan [email protected]