Dendritic Cell Interactions with Bacteria

Emerging evidence suggests that dendritic cells play a major role in the orchestration of the immune response to bacteria. This book introduces the reader to the complex world of dendritic cells and describes how the intimate interplay between dendritic cells, bacteria and the environment dictates either the induction of immunity or tolerance to the encountered microorganisms. It discusses how this can allow organisms to tolerate beneficial bacteria and to react against pathogens, as well as the strategies pathogenic bacteria have evolved to escape dendritic cell patrolling. Expert contributors discuss everything from bacterial capture and recognition to their killing, processing and the induction of adaptive immunity. Particular focus is on the tissue context in which bacteria are handled by dendritic cells and on possible defects therein, which may potentially lead to chronic infection or inflammation. Graduate students and researchers will find this an invaluable overview of current dendritic cell biology research.

MARIA RESCIGNO is the Director of the Immunobiology of Dendritic Cells and Immunotherapy Research Unit at the European Institute of Oncology, Milan, Italy.

Published titles

  1 Bacterial Adhesion to Host Tissues. Edited by Michael Wilson 0521801079
  2 Bacterial Evasion of Host Immune Responses. Edited by Brian Henderson and Petra Oyston 0521801737
  3 Dormancy in Microbial Diseases. Edited by Anthony Coates 0521809401
  4 Susceptibility to Infectious Diseases. Edited by Richard Bellamy 0521815258
  5 Bacterial Invasion of Host Cells. Edited by Richard Lamont 0521809541
  6 Mammalian Host Defense Peptides. Edited by Deirdre Devine and Robert Hancock 0521822203
  7 Bacterial Protein Toxins. Edited by Alistair Lax 052182091X
  8 The Dynamic Bacterial Genome. Edited by Peter Mullany 0521821576
  9 Salmonella Infections. Edited by Pietro Mastroeni and Duncan Maskell 0521835046
10 The Influence of Cooperative Bacteria on Animal Host Biology. Edited by Margaret McFall Ngai, Brian Henderson and Edward Ruby 0521834651
11 Bacterial Cell-to-Cell Communication. Edited by Donald R. Demuth and Richard Lamont 0521846382
12 Phagocytosis of Bacteria and Bacterial Pathogenicity. Edited by Joel Ernst and Olle Stendahl 0521845696
13 Bacterial-Epithelial Cell Cross-Talk: Molecular Mechanisms in Pathogenesis. Edited by Beth A. McCormick 0521852447

ADVANCES IN MOLECULAR AND CELLULAR MICROBIOLOGY (AMCM)

Over the past decade, the rapid development of an array of techniques in the fields of cellular and molecular biology has transformed whole areas of research across the biological sciences. Microbiology has perhaps been influenced most of all. Our understanding of microbial diversity and evolutionary biology, and of how pathogenic bacteria and viruses interact with their animal and plant hosts at the molecular level, for example, have been revolutionized. Perhaps the most exciting recent advance in microbiology, a fusion of classical microbiology, microbial molecular biology and eukaryotic cellular microbiology. Cellular microbiology is revealing how pathogenic bacteria interact with host cells in what is turning out to be a complex evolutionary battle of competing gene products. Molecular and cellular biology are no longer discrete subject areas but vital tools and an integrated part of current microbiological research. As part of this revolution in molecular biology, the genomes of a growing number of pathogenic and model bacteria have been fully sequenced, with immense implications for our future understanding of microorganisms at the molecular level.

  Advances in Molecular and Cellular Microbiology is a series edited by researchers active in these exciting and rapidly expanding fields. Each volume will focus on a particular aspect of cellular or molecular microbiology and will provide an overview of the area, as well as examine current research. This series will enable graduate students and researchers to keep up with the rapidly diversifying literature in current microbiological research.

Series Editors

Professor Brian Henderson
University College, London

Professor Michael Wilson
University College, London

Professor Sir Anthony Coates
St George’s Hospital Medical School, London

Professor Michael Curtis
St Bartholomew’s and Royal London Hospital, London

Advances in Molecular and Cellular Microbiology 14

Dendritic Cell Interactions with Bacteria

EDITED BY
MARIA RESCIGNO
European Institute of Oncology

CAMBRIDGE UNIVERSITY PRESS
Cambridge, New York, Melbourne, Madrid, Cape Town, Singapore, São Paulo

Cambridge University Press
The Edinburgh Building, Cambridge CB2 8RU, UK

Published in the United States of America by Cambridge University Press, New York

www.cambridge.org
Information on this title: www.cambridge.org/9780521855860

© Cambridge University Press 2007

This publication is in copyright. Subject to statutory exception and to the provisions of relevant collective licensing agreements, no reproduction of any part may take place without the written permission of Cambridge University Press.

First published 2007

Printed in the United Kingdom at the University Press, Cambridge

A catalogue record for this publication is available from the British Library

Library of Congress Cataloging in Publication data

Dendritic cell interactions with bacteria/edited by Maria Rescigno.
  p. ; cm. – (Advances in molecular and cellular microbiology; 14)
Includes bibliographical references and index.
ISBN-13: 978-0-521-85586-0 (hardback)
1. Dendritic cells. 2. Bacteria. 3. Host-bacteria relationships. 4. Bacterial diseases–Immunological aspects. I. Rescigno, Maria, 1968-II. Title. III. Series.
[DNLM: 1. Dendritic Cells–immunology. 2. Bacteria–immunology. 3. Bacterial Infections–immunology. QW 568 D3905 2007]
QR185.8.D45D452 2007
616.07'9–dc22                       2006020611

Cambridge University Press has no responsibility for the persistence or accuracy of URLs for external or third-party Internet websites referred to in this publication, and does not guarantee that any content on such websites is, or will remain, accurate or appropriate.

Contents

Preface

Dendritic cells (DCs) comprise a family of professional antigen presenting cells that are unique in their ability to activate T lymphocytes. Dendritic cells patrol all the tissues at the interface with the external world, including skin and mucosal surfaces, for the presence of invaders. The DC system is characterized by a remarkable plasticity that allows the induction both of immunity and tolerance toward the encountered antigens. This is achieved through the combination of a number of different factors, including the subsets of DCs, their activation state and environmental cells that can regulate DC function. DCs are present in the periphery in an immature form that is particularly apt at capturing antigens and at deciphering the messages associated therein. After an activation stimulus that is delivered by some antigens (including bacteria) or by inflammatory cytokines released during inflammation, activated DCs acquire a migratory phenotype and reach the draining lymph node. Here, DCs present the antigens captured in the periphery and initiate T cell adaptive immune responses.

This book describes how the intimate interplay between dendritic cells, bacteria and the environment dictates the induction of immunity or tolerance to bacteria and how pathogenic bacteria have evolved strategies to escape DC patrolling. The first section introduces the complexity of the DC system describing the different subpopulations of DCs and their role in the induction of immune responses. This is followed by the description of a class of pathogen recognition receptors and their signaling pathways that are fundamental in the activation of DCs after recognition of bacterial structural components. These receptors, belonging to the Toll-like receptor family, are differentially expressed on DC subpopulations and contribute to generate functional diversity. To conclude this general part on DC function, there is a description on how bacterial antigens are handled, processed and presented by DCs.

In the second section, attention switches to the role of DCs in the initiation and orchestration of innate immune responses. The section begins describing how dendritic cells can directly participate in the uptake of bacteria across mucosal surfaces and its consequences in terms of DC activation. After microbial recognition, DCs act first as innate immune cells that release inflammatory mediators that can strengthen and amplify the innate immune response. In particular a novel monocyte-derived DC population called TipDCs that produces large amounts of tumor necrosis factor (TNF) and inducible nitric oxide synthase (iNOS) is reported. Then DCs can leave the infected site to reach the draining lymph node for T cell activation. Thus, DCs represent a link between innate and adaptive immunity because their activation can lead on one side to the recruitment and activation of innate immune cells like granulocytes, macrophages and natural killer (NK) cells and on the other side to the activation of adaptive immune cells. To achieve this, DCs can act on their own or in concert with other innate immune cells like NK cells, as discussed in the last chapter of this section.

The following section deals with the initiation of adaptive immune responses that is conducted by DCs that have deciphered and integrated signals deriving from the bacteria, the infected tissue and the recruited immune cells. Two major examples of DC handling of strictly or facultative intracellular bacteria have been considered, namely Legionella and Salmonella. It is described how differently from macrophages, DCs have evolved strategies to handle and control intracellular growth of Legionella and to activate effective adaptive immune responses to control bacterial infection. Interestingly, DCs can present bacterial antigens also when they are non-infected after phagocytozing infected cells. This process also known as cross-presentation is unique to DCs and favors the activation of T cell responses toward Salmonella, Listeria and Mycobacterium.

Finally, strategies developed by bacteria to evade DC recognition and activation are discussed in the fourth section. Here pathogen recognition receptors are thoroughly discussed as possible targets for pathogens to modulate immune function of antigen presenting cells. It is described that the cross-talk between different classes of pathogen recognition receptors can lead to suppression or activation of immune responses. In the following chapter the ability of bacteria or their products to suppress the immune response through the skewing of T cell responses toward regulatory T cells or to subtypes which are inappropriate for bacterial elimination is reported. A major drawback of improper bacterial handling can result in chronic inflammatory responses particularly at sites continuously exposed to bacteria like the gut. Here, commensal bacteria are beneficial to the host as they help digesting ingested food through the degradation of complex sugars and metabolites. In order to tolerate “good” bacteria, the immune system has developed strategies to cohabitate with beneficial bacteria and discriminate harmful pathogens. When these strategies are disrupted, inflammatory responses can arise leading to inflammatory bowel disease as discussed in the last chapter of this section.

In conclusion, this book has brought together experts in several fields of dendritic cell–bacteria interaction from their capture and recognition to their killing, processing and induction of adaptive immunity. Much attention has been focused on the tissue context where bacteria are handled by DCs. When defects either in bacterial handling or in the interaction with the environment are encountered, chronic infection or inflammation can arise.

Abbreviations

Contributors

Shizuo Akira
Department of Host Defense
Research Institute for Microbial Diseases
Osaka University
3-1 Yamada-oka
Suita
Osaka 565-0871
Japan and
ERATO, Japan Science and Technology Agency
3-1 Yamada-oka
Suita
Osaka 565-0871
Japan

Carlos Ardavín
Department of Immunology and Oncology
Centro Nacional de Biotecnologia/CSIC
Universidad Autònoma
28049 Madrid
Spain

Christoph Becker
I Department of Medicine
University of Mainz
55131 Mainz
Germany

Laurence Bougnères-Vermont
Institut Curie
Inserm u653
26 rue d’Ulm
75248 Paris
cedex 05
France

Miriam T. Brady
Immune Regulation Research Group
School of Biochemistry and Immunology
Trinity College
Dublin 2
Ireland

Anneke Engering
Department of Molecular Cell Biology and Immunology
VU Medical Center
v.d. Boechorststraat 7
1081 BT Amsterdam
The Netherlands

Guido Ferlazzo
Istituto Nazionale Ricerca sul Cancro
Genoa
Italy and
University of Messina
Messina 98100
Italy

Teunis B. H. Geijtenbeek
Department of Molecular Cell Biology and Immunology
VU Medical Center
v.d. Boechorstraat 7
1081 BT Amsterdam
The Netherlands

Pierre Guermonprez
Institut Curie, inserm u653
26 rue d’Ulm
75248 Paris
cedex 05
France

Estella A. Koppel
Department of Molecular Cell Biology and Immunology
VU Medical Center
v.d. Boechorststraat 7
1081 BT Amsterdam
The Netherlands

Peter McGuirk
Opsona Therapeutics
Biotechnology Building
Trinity College
Dublin
Ireland

Kingston H. G. Mills
Immune Regulation Research Group
School of Biochemistry and Immunology
Trinity College
Dublin 5
Ireland

Catarina Nogueria
Section of Microbial Pathogenesis
Yale University School of Medicine
Boyer Center for Molecular Medicine
295 Congress Avenue
New Haven
CT 06536

Eric G. Pamer
Infectious Diseases Service
Memorial Sloan-Kettering Cancer Center
Immunology Program
Sloan Kettering Institute
1275 York Avenue
New York
New York 10021
USA

Maria Rescigno
European Institute of Oncology
Department of Experimental Oncology
Via Ripamonti 435
20141 Milan
Italy

Craig R. Roy
Section of Microbial Pathogenesis
Yale University School of Medicine
Boyer Center for Molecular Medicine
295 Congress Avenue
New Haven
CT 06536
USA

Natalya V. Serbina
Infectious Diseases Service
Memorial Sloan-Kettering Cancer Center
Immunology Program
Sloan Kettering Institute
1275 York Avenue
New York
New York 10021
USA

Sunny Shin
Section of Microbial Pathogenesis
Yale University School of Medicine
Boyer Center for Molecular Medicine
295 Congress Avenue
New Haven
CT 06536
USA

Osamu Takeuchi
Department of Host Defense
Research Institute for Microbial Diseases
Osaka University and
ERATO,
Japan Science and Technology Agency
3-1 Yamada-oka
Suita
Osaka 565-0871
Japan

Yvette van Kooyk
Department of Molecular Cell Biology and Immunology
VU Medical Center
v.d. Boechorststraat 7
1081 BT Amsterdam
The Netherlands

Sandra J. van Vliet
Department of Molecular Cell Biology and Immunology
VU Medical Center
v.d. Boechorststraat 7
1081 BT Amsterdam
The Netherlands

Mary Jo Wick
Department of Microbiology and Immunology
Göteborg University
Box 435
SE 40530 Göteborg
Sweden