Biological DNA Sensor. The Impact of Nucleic Acids on Diseases and Vaccinology

347 Pages·2014·11.42 MB·English

by  Ken Ishii and Choon Kit Tang (Eds.)

BIOLOGICAL DNA
SENSOR
The Impact of Nucleic
Acids on Diseases and
Vaccinology
BIOLOGICAL DNA
SENSOR
The Impact of Nucleic
Acids on Diseases and
Vaccinology
KEN J. ISHII
Vaccine Science Laboratory, Immunology Frontier Research Centre (IFReC),
Osaka University, Osaka, Japan
and
Laboratory of Adjuvant Innovation, National Institute of Biomedical
Innovation (NIBIO), Osaka, Japan
CHOON KIT TANG
Vaccine Science Laboratory, Immunology Frontier Research Centre (IFReC),
Osaka University, Osaka, Japan
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LIST OF CONTRIBUTORS
Shizuo Akira
Host Defense Laboratory, IFReC, Osaka University, Japan
Moshe Arditi
Department of Biomedical Sciences and Pediatric Infectious Diseases and Immunology,
Cedars-Sinai Medical Center; Infectious and Immunologic Diseases Research Center,
Cedars-Sinai Medical Center, Los Angeles, CA; David Geffen School of Medicine,
University of California at Los Angeles, USA
Glen N. Barber
Department of Cell Biology and Sylvester Comprehensive Cancer Center, University of
Miami Miller School of Medicine, Miami, FL, USA
Andrew G. Bowie
School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity
College Dublin, Ireland
Michael P. Cancro
Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the
University of Pennsylvania, Philadelphia, PA, USA
Cevayir Coban
Laboratory of Malaria Immunology, WPI Immunology Frontier Research Center (IFReC),
Osaka University, Osaka, Japan
Timothy R. Crother
Department of Biomedical Sciences and Pediatric Infectious Diseases and Immunology,
Cedars-Sinai Medical Center; Infectious and Immunologic Diseases Research Center,
Cedars-Sinai Medical Center, Los Angeles, CA; David Geffen School of Medicine,
University of California at Los Angeles, USA
Christophe J. Desmet
Laboratory of Cellular and Molecular Immunology, Interdisciplinary Cluster of Applied
Genoproteomics (GIGA) – Research Center and Faculty of Veterinary Medicine,
University of Liège, Liège, Belgium
Katherine A. Fitzgerald
Division of Infectious Diseases and Immunology, Department of Medicine, University of
Massachusetts Medical School, Worcester, MA, USA
S. Gasser
Immunology Programme and Department of Microbiology, Centre for Life Science,
National University of Singapore, Singapore
S.W.S. Ho
Immunology Programme and Department of Microbiology, Centre for Life Science,
National University of Singapore, Singapore
xi
xii List of Contributors
Ken J. Ishii
Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation (NIBIO),
Saito-Asagi, Ibaraki City, Osaka, Japan; Vaccine Science Laboratory, Immunology Frontier
Research Centre (IFReC), Osaka University, Japan
Nao Jounai
Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation, Osaka,
Japan
Taro Kawai
Laboratory of Host Defense, WPI Immunology Frontier Research Center, Department of
Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
Kouji Kobiyama
Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation, Osaka,
Japan
C.X. Koo
Immunology Programme and Department of Microbiology, Centre for Life Science,
National University of Singapore, Singapore; Laboratory of Adjuvant Innovation, National
Institute of Biomedical Innovation (NIBIO), Ibaraki, Osaka, Japan
A.R. Lam
Immunology Programme and Department of Microbiology, Centre for Life Science,
National University of Singapore, Singapore
N. Le Bert
Immunology Programme and Department of Microbiology, Centre for Life Science,
National University of Singapore, Singapore
Laurel L. Lenz
Integrated Department of Immunology, National Jewish Health and University of
Colorado School of Medicine, Denver, CO, USA
Ann Marshak-Rothstein
Department of Medicine/Rheumatology, University of Massachusetts Medical School,
Worcester, MA, USA
Jan Naujoks
Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité
Universitätsmedizin Berlin, Berlin, Germany
Bastian Opitz
Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité
Universitätsmedizin Berlin, Berlin, Germany
Søren R. Paludan
Department of Biomedicine, Aarhus Research Center for Innate Immunology, University
of Aarhus, The Bartholin Building, Aarhus C, Denmark
Surya Pandey
Laboratory of Host Defense, WPI Immunology Frontier Research Center, Department
of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka,
Japan
List of Contributors xiii
Vijay A.K. Rathinam
Division of Infectious Diseases and Immunology, Department of Medicine, University of
Massachusetts Medical School, Worcester, MA, USA
Tatsuya Saitoh
Department of Host Defense, Research Institute for Microbial Diseases, Osaka University,
Suita, Osaka, Japan; Laboratory of Host Defense, WPI Immunology Frontier Research
Center, Osaka University, Suita, Osaka, Japan
Rebecca Schmidt
Integrated Department of Immunology, National Jewish Health and University of
Colorado School of Medicine, Denver, CO, USA
Y.J. Shen
Immunology Programme and Department of Microbiology, Centre for Life Science,
National University of Singapore, Singapore
Kenichi Shimada
Department of Biomedical Sciences and Pediatric Infectious Diseases and Immunology,
Cedars-Sinai Medical Center; Infectious and Immunologic Diseases Research Center,
Cedars-Sinai Medical Center, Los Angeles, CA; David Geffen School of Medicine,
University of California at Los Angeles, USA
Fumihiko Takeshita
Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation,
Osaka, Japan
Choon Kit Tang
Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation
(NIBIO), Saito-Asagi, Ibaraki City, Osaka, Japan; Laboratory of Malaria Immunology,
WPI Immunology Frontier Research Center (IFReC), Osaka University, Osaka, Japan;
Laboratory of Vaccine Science, IFReC, Osaka University, Osaka, Japan
Miyuki Tozuka
Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation,
Osaka, Japan
Sivapriya Kailasan Vanaja
Division of Infectious Diseases and Immunology, Department of Medicine, University of
Massachusetts Medical School, Worcester, MA, USA; Department of Molecular Biology
and Microbiology, Tufts School of Medicine, Boston, MA, USA
PREFACE
Deoxyribonucleic acid (DNA), the fundamental molecule that packs
genetic instructions for the development of living organisms, has been dis-
covered to hold yet another vital function for our biology – inflammation.
The fact that DNA is an abundant commodity in our body and causes its
immunogenic property is one that cannot be taken lightly. Now, we know
that DNA induced inflammation is responsible for the pathogenicity of
autoimmune and infectious diseases and metabolic disorders. Furthermore,
we have evidence that DNA induced inflammation is involved in the
development of cancer. Therefore the awareness of the immunogenic
nature of dsDNA has provided us with the opportunity to gain further
insights into the workings of human diseases. DNA seemed to be an
ironic choice as a trigger molecule for inflammation. After all, who would
expect that self-products containing our genetic blueprint could turn
against us and induce adverse inflammatory reactions upon detection by
the immune system? However, on deeper reflection, it does make practi-
cal sense to have nucleic acids as signaling entities that sound off the alarm
to indicate impending danger to the body. Pathogens including viruses,
bacteria and parasites, like human beings, have their genetic information
stored in nucleic acids. Their invasion into the host system is likely to be
associated with the introduction of their genetic materials and therefore
it would be the most appropriate indication of pathogenic invasion. On
the other hand, the release of our own DNA into the surrounding physi-
ological environment could also indicate cell death as a result of trauma,
which may invite infection to occur and require immune defenses to be
put in place. Therefore in more ways than one, DNA is an aptly chosen
alarm molecule for the immune system to react to danger. Regarding the
potential impact it has on various aspects of our health, we have seen an
explosion of research on DNA sensing in the past eight years. This surge
in publication was due in part to the discovery that DNA could be sensed
not only by TLR9 in the endosomes, but also by sensors present in the
cytosol. More importantly, DNA from pathogens as well as from mamma-
lian derived sources is equally potent in inducing inflammation.
It is the purpose of this book to bring together the research on the
signaling mechanism of DNA induced inflammation as well as its impact
on diseases and vaccinology. The book has three sections: In Section I,
xv
xvi Preface
Ishii, Fitzgerald, Barber and Saitoh discuss the signaling pathway leading
to DNA induced inflammation, in Section II, Kawai, Marshak-Rothstein,
Opitz, Bowie, Gasser and Arditi discuss the impact of DNA inflamma-
tion on human diseases and lastly, in Section III, Coban, Desmet and Lenz
comment on how the inflammatory response of DNA could influence the
outcome of vaccination in DNA vaccination strategies and adjuvants tar-
geting the DNA sensing pathway.
We are greatly indebted to the contributors whose participation and
cooperation made this book possible. We thank them for their patience
with our persistent requests for completion of their manuscript. We are
appreciative for the editorial and technical assistance provided by Elizabeth
Gibson and Mary Preap. To the publisher we are grateful for this timely
opportunity to consolidate the wealth of knowledge we have acquired on
DNA sensing which could facilitate future investigations. Lastly, we would
like to pay tribute to Alick Issacs and his colleagues who were way ahead
of their time in that they had the audacity to identify a molecule that
is so fundamental to our existence, namely, DNA, as a danger signaling
molecule.
1
CHAPTER
Route to Discovering the
Immunogenic Properties of DNA
from TLR9 to Cytosolic DNA Sensors
Choon Kit Tang1,2,3,4, Cevayir Coban2, Shizuo Akira3 and Ken J. Ishii1,4
1Vaccine Science Laboratory, Immunology Frontier Research Centre (IFReC), Osaka University, Japan
2Malaria Immunology Laboratory, IFReC, Osaka University, Japan
3Host Defense Laboratory, IFReC, Osaka University, Japan
4Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation (NIBIO), Saito-Asagi,
Osaka, Japan
INTRODUCTION
The innate immune system relies on cues in the form of products released
during injury or pathogenic invasion for its activation. Immunologists have
come to appreciate deoxyribonucleic acid (DNA) as one of such products
that signal danger to the innate immune system and induce inflammation.
For example, uncleared DNA released during mechanical injury to tissues
or the introduction of viral and bacterial DNA during infection was found
to elicit inflammatory responses. This immune response induced by DNA is
not a random process but rather it is detected by specific receptors that trig-
ger distinct cell signaling pathways to produce inflammatory products. Our
journey in understanding the mechanism of DNA sensing and inflamma-
tion began with the discovery of Toll-like receptor 9 (TLR9) in endosomal
compartments and its ability to detect CpG motifs present specifically in
the DNA of microbes. The immune response generated by TLR9 detec-
tion of CpG DNA is potent and capable of protection against pathogenic
infection and it was also studied for applications in vaccine adjuvants. It was
realized however that TLR9 could not be the sole DNA sensor present in
the cell as inflammation induced by DNA persisted despite the absence
of TLR9. This was not clearly understood until it was realized that DNA
when directly introduced into the cytosol of cells could elicit potent type-
I-interferon (type-I-IFN) responses that were independent of TLR9 but
completely relied on the TBK1–IRF3 signaling axis. This discovery led to
the conclusion that there are other sensors of DNA present in the cytosol
and not in the endosomal compartments which could induce inflammation.
Biological DNA Sensor. © 22001144 Elsevier Inc.
DOI: http://dx.doi.org/10.1016/B978-0-12-404732-7.00001-0 All rights reserved. 3
4 Immunogenic Properties of DNA from TLR9 to Cytosolic DNA Sensors
Figure 1.1 The current understanding of the DNA sensing pathways. Yellow oval buttons
depict identified DNA sensors; blue and pink square buttons are the signaling/adaptor
molecules and transcription factors involved in the particular pathway; purple tubes
are ◢ positive and ◣ negative regulators of the pathways.
Since then, several cytosolic DNA sensors have been published and more
continue to be reported (Figure 1.1). In this chapter, we will reflect on our
early understanding of the immunogenic properties of dsDNA and give a
chronological account of the journey we have taken to discover the indi-
vidual cellular DNA sensors that have played important roles in mediating
DNA induced inflammation.
THE IMPORTANCE OF THE INNATE IMMUNE SYSTEM
PAMPS and DAMPs
The immune responses of higher animals can be broadly categorized into
those of the innate immune system and the adaptive immune system. They
differ in the cell types and cytokines involved as well as the level of speci-
ficity and most importantly the responding time. Adaptive immunity pro-
vides protection with high degree of specificity and efficiency by targeting
antigens present on the invading pathogen. This is put in place through a