Microbial DNA and host immunity

427 Pages·2002·4.885 MB·English

by  E Raz

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Microbial DNA and Host Immunity

Microbial DNA
and Host Immunity
Edited by
Eyal Raz,
MD
University of California, San Diego
La Jolla, CA
Humana Press Totowa, New Jersey
© 2002 Humana Press Inc.
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Library of Congress Cataloging-in-Publication Data
Microbial DNA and host immunity / edited by Eyal Raz
p. ; cm.
Includes bibliographical references and index.
ISBN 1-58829-022-0 (alk. paper)
[DNLM: 1. DNA, Bacterial--immunology. 2. Adjuvants, Immunologic. 3. Vaccines.
QW 52 M6238 2003]
Qr186.6 B33 M535 2003
616'.014--dc21
2002068938
Dedication
In memory of my dear parents, Miriam and Chaim Raz.

Preface
The observation that bacterial DNA, or its synthetic immuno-
stimulatory oligonucleotide (ISS-ODN) analogs containing unmethylated
CpG dinucleotide, are potent activators of innate immunity has attracted
a wide spectrum of scientists with interest in basic and/or translational
research. Like other microbial products, e.g., peptidoglycans, lipopeptides,
lipopolysaccharides, or dsRNA, bacterial DNA triggers its immune prop-
erties via a member of the TLR family (i.e., TLR9). These immune prop-
erties are aimed mainly at providing an immediate defense mechanism in
the mammalian host. Bacterial DNA stimulates the production of type-1
cytokines such as IL-12 and IFNs, and enhances the expression of vari-
ous co-stimulatory ligands such as B7, CD40, and ICAM-1, as well as
class I and class II MHC molecules, mainly by and on antigen presenting
cells. This wide range of activities contributes to the use of ISS-ODN as a
unique adjuvant that induces both Th1 and CTL responses to experimen-
tal and relevant clinical antigens. To date, ISS-ODN has been used as an
adjuvant in a variety of clinical trials in the fields of infectious disease,
allergy, and cancer. Recent data also identified unique immunomodulating
properties and antiinflammatory activities induced by ISS-ODN in an
antigen-independent fashion. These inhibit allergic inflammation and coli-
tis in various animal models, respectively.
Based on the progress made to date in uncovering the basic bio-
logical principles of immune activation by immunostimulatory DNA
and the initial encouraging data emerging from related clinical trials, it
is predicted that more efforts will be invested in this field by both
academia and industry. It is anticipated that in next few years, our knowl-
edge of this area will be further expanded and that potentially impor-
tant applications derived from this understanding will find their way to
various aspects of clinical medicine.
I wish to thank all the authors and their colleagues for their contribu-
tions, the editors for their help and support, and Jane Uhle for her determi-
nation and help in putting this book together in a relatively short time.
Eyal Raz, MD
vii

Contents
Preface................................................................................................... vii
Contributors......................................................................................... xiii
P I: I
ART NTRODUCTION
1 Immunostimulatory DNA:
An Overview
Eyal Raz.........................................................................3
2 Historical Perspectives
Saburo Yamamoto, Toshiko Yamamoto,
and Tohru Tokunaga ................................................9
P II: R S
ART ECEPTORS AND IGNALING
3 Signal Transduction Pathways Activated By CpG-DNA
Hans Häcker................................................................17
4 A Novel Toll-Like Receptor that Recognizes Bacterial DNA
Hiroaki Hemmi and Shizuo Akira.............................39
5 Activation of Innate Immunity by Microbial Nucleic Acids
Wen-Ming Chu, Xing Gong, and Tony Yoon ............49
6 Phosphorothioate Backbone Modification Changes
the Pattern of Responses to CpG
Katryn J. Stacey, David P. Sester, Shalin Naik,
Tara L. Roberts, Matthew J. Sweet,
and David A. Hume.................................................63
P III: C A
ART ELL CTIVATION
7 Activation of NK Cell By Immunostimulatory
Oligo-DNA in Mouse and Human
Saburo Yamamoto, Toshiko Yamamoto,
Tetsuro Kataoka, Sumiko Iho,
and Tohru Tokunaga ..............................................81
ix