Nucleic Acids in Innate Immunity

304 Pages·2008·4.5 MB·English

by  Ken J. Ishii

Nucleic
Acids
in
Innate
Immunit y

Nucleic
Acids
in
Innate
Immunit y
Edited by
Ken J. Ishii
Shizuo Akir a
Boca Raton London New York
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Library of Congress Cataloging-in-Publication Data
Nucleic acids in innate immunity / [edited by] Ken J. Ishii and Shizuo Akira.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-1-4200-6825-2 (alk. paper)
1. Natural immunity. 2. Nucleic acids. I. Ishii, Ken J. II. Akira, S. III. Title.
[DNLM: 1. Immunity, Natural--physiology. 2. Autoimmunity. 3.
DNA--immunology. 4. RNA--immunology. 5. Receptors, Pattern
Recognition--immunology. 6. Self Tolerance. QW 541 N964 2008]
QR185.2.N82 2008
616.07’9--dc22 2007047405
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Contents
Preface......................................................................................................................vii
Editors .......................................................................................................................xi
Contributors ...........................................................................................................xiii
Section I
Roles of Nucleic Acids in Immunity
Chapter 1 Structural Analysis of Toll-Like Receptors .........................................3
Jungwoo Choe and Ian A. Wilson
Chapter 2 Antiviral Signaling through TLRs and RLHs ...................................17
Taro Kawai
Chapter 3 Recognition of Virus Invasion by Toll-Like Receptors and RIG-
I-Like Helicases ..................................................................................31
Hiroki Kato and Osamu Takeuchi
Chapter 4 Characteristics of Dendritic Cell Responses to Nucleic Acids ..........43
Tsuneyasu Kaisho, Takahiro Sugiyama, and Katsuaki Hoshino
Chapter 5 Dendritic Cells as Sensors for Foreign and Self Nucleic Acids .........59
Anne Krug and Wolfgang Reindl
Section II
Mechanisms and Therapeutic Applications of Immunomodulatory DNA
Chapter 6 Natural DNA Recognition by Toll-Like Receptor 9 Does Not
Rely upon CpG Motifs: Role of Endosomal Compartmentation .......77
Tobias Haas, Frank Schmitz, Antje Heit, and Hermann Wagner
Chapter 7 Discrimination of Self and Non-Self DNAs ......................................85
Katryn J. Stacey, Francis Clark, Greg R. Young, Tara L. Roberts
v
vi Nucleic Acids in Innate Immunity
Chapter 8 Therapeutic Potential of Immunosuppressive Oligonucleotides
Expressing TTAGGG Motifs ...........................................................101
Dennis M. Klinman, Debbie Currie, Chiaki Fujimoto, Igal
Gery, and Hidekazu Shirota
Chapter 9 Structure/Function of IFNα-Inducing CpG ODNs ..........................113
Daniela Verthelyi and Montserrat Puig
Chapter 10 Clinical Development of Oligodeoxynucleotide TLR9 Agonists ....129
Julie L. Himes and Arthur M. Krieg
Chapter 11 Prospects for TLR9-Based Immunotherapy for Asthma
and Allergy .......................................................................................145
David Broide
Chapter 12 Toll-Like Receptors in Development of Systemic Autoimmune
Disease: In Vitro Artifact or In Vivo Paradigm? ..............................159
Ann Marshak-Rothstein and Mark J. Shlomchik
Chapter 13 Impacts of Nucleoside Modification on RNA-Mediated
Activation of Toll-Like Receptors ....................................................171
Katalin Karikó and Drew Weissman
Chapter 14 Activation of Innate Pattern Recognition Pathways by Single-
Stranded Ribonucleic Acids .............................................................189
Sandra S. Diebold
Chapter 15 RNA Interference in Scope of Immune System ...............................207
Andrea Ablasser, Gunther Hartmann, and Veit Hornung
Chapter 16 Recognition of RNA and Synthetic Compounds by TLR7
and TLR8 .........................................................................................227
Svetlana Hamm and Stefan Bauer
Chapter 17 Helicases at Frontline of RNA Virus Recognition ...........................241
Leonid Gitlin and Marco Colonna
Index ......................................................................................................................273
Preface
All living organisms are continuously exposed to foreign entities including food,
microorganisms, and unnecessary self-metabolites, thus creating a need to discrimi-
nate dangerous non-self from safe self entities, particularly life-threatening micro-
organisms that invade the body. The vertebrate immune system has evolved two
arms of defense against invading pathogens: innate (natural) immunity and adaptive
(acquired) immunity. A great deal of immunology research revealed that adaptive
immunity has two sophisticated systems designated self- and non-self-discrimina-
tion by which T and B cells, both of which express highly diverse antigen receptors
generated through DNA rearrangement, are thereby able to respond to a wide range
of potential antigens.
In contrast, innate immunity had been regarded as a relatively non-specific sys-
tem whose two main roles were engulfing and destroying pathogens. The innate
system also triggers pro-inflammatory responses and is involved in antigen presenta-
tions to prime adaptive immune responses.
Recent studies have shown that the innate immune system has a greater degree
of specificity than was previously thought. The system has a highly developed abil-
ity to discriminate between self and foreign entities, including microorganisms and
unnecessary self molecules including proteins, and lipids, as well as nucleic acids
that constitute the main topic of this book. Why and how the innate immune system
discriminates self and non-self nucleic acids will be discussed in particular detail by
the groups of Wagner and Stacey (DNA) and Kariko, Diebold, Hornung, Bauer, and
Colonna (RNA).
This discrimination relies, to a great extent, on pattern-recognition receptors
(PRRs) including Toll-like receptors (TLRs), Nod-like receptors (NLRs) and the
recently described RIG-I-like receptors (RLRs) that play a crucial role in early host
defenses against invading pathogens, as described in the chapters contributed by the
groups of Wilson, Kawai, Kato, Kaisho and Krug. These germ line-encoded PRRs
are expressed constitutively on both immune and non-immune cells, and recognize
conserved microbial components known as pathogen-associated molecular patterns
(PAMPs).1 After recognition, each PRR activates specific signaling pathways, lead-
ing to robust but highly defined innate immune responses, followed by protective
adaptive (antigen-specific) immune responses to pathogens.
PAMPs have triggered considerable interest in nucleic acids in the field of
immunology. While nucleic acids such as DNA and RNA are essential components
of all living organisms, accumulating evidence over the last several decades sug-
gests that nucleic acids function as essential ultimate units of life and also stimulate
the immune system when they are released from pathogens.2,3 Their connection to
pathogens attracted little attention in the past, but the link is in the limelight after the
recent discovery of TLRs.4,5
Structure- and sequence-dependent immune recognitions of nucleic acids by
TLRs were shown to play an important role in both innate and adaptive immune
vii
viii Nucleic Acids in Innate Immunity
responses to infectious organisms, including bacteria, viruses, and parasites.6,7 Novel
therapeutics include nucleic acid-based agonists and antagonists via TLR-mediated
immunomodulation, and including the use of CpG DNA as a potent TLR9 agonist are
under development for multiple applications to prevent or treat infectious diseases,
allergic disorders, and cancers (detailed by Krieg, Verthelyi, Klinman and Broide).
On the other hand, the innate immune system that fights infection also seems to
have an important role in clearing unnecessary or abnormal host molecules includ-
ing nucleic acids. In fact, the system possesses specialized sets of genes including
TLRs that facilitate clearance in cases of trauma, tumor, and autoimmune diseases,8,9
as summarized in the chapter by Rothstein. This role of the innate immune sys-
tem is important. Initial dogma dictating that the system including TLRs discrimi-
nates infectious non-self from non-infectious self nucleic acids has been challenged
by findings that host (self) nucleic acids are no longer inert in the immune system
under certain conditions. Thus, the one or more elements within DNA and RNA
(sequence, modification, structure) recognized by the innate immune system con-
stitute an important issue that must be clarified to further explain this system. This
book reviews recent advances in our understanding of the innate immune recogni-
tion of nucleic acids, and describes the resulting immune modulation through TLR-
dependent or -independent pathways.
We would like to acknowledge some of the pioneering works that appeared long
before the studies in this book were published. In 1963, two independent groups,
including one led by Alick Isaacs who discovered interferon, reported that DNA and
RNA derived from pathogens or host cells activated chicken and mouse fibroblasts
to produce interferon (IFN).11 The other pioneering work in 1984 by Tokunaga and
colleagues showed that a DNA fraction isolated from BCG activated both human and
mouse non-B, non-T cells to produce type I IFNs.12 They also demonstrated that bac-
terial, and not mammalian, DNAs are immunostimulatory and can be reproduced by
short, single-stranded (ss) oligodeoxyribonuleotides (ODNs) containing palindromic
GC-rich sequences.13
Finally, we hope that our book will provide insight into the new areas of immu-
nology, nucleic acid recognition, and regulation by innate immune systems.
Ken J. Ishii and Shizuo Akira
Research Institute for Microbial Diseases
Osaka University
RefeRences
1. C. A. Janeway, Jr. and R. Medzhitov, Annu .Rev. Immunol. 20, 197 (2002).
2. A. Isaacs, R. A. Cox, and Z. Rotem, Lancet 2, 113 (1963).
3. T. Tokunaga, T. Yamamoto, and S. Yamamoto, Jpn. J. Infect. Dis. 52, 1 (1999).
4. R. Medzhitov and C. A. Janeway, Jr., Science 296, 298 (2002).
5. S. Akira and K. Takeda, Nat. Rev. Immunol. 4, 499 (2004).
6. H. Wagner, Trends Immunol. 25, 381-386 (2004).
7. K. J. Ishii and S. Akira, Trends Immunol. 27, 525 (2006).
8. P. Matzinger, Science 296, 301 (2002).
Preface ix
9. B. Beutler, Nature 430, 257 (2004).
10. Z. Rotem, R. A. Cox, and A. Isaacs, Nature 197, 564 (1963).
11. K. E. Jensen, A. L. Neal, R. E. Owens, and J. Warren, Nature 200, 433 (1963).
12. T. Tokunaga et al., J. Natl. Cancer Inst. 72, 955 (1984).
13. S. Yamamoto et al., J. Immunol. 148, 4072 (1992).