Contents

Contributors

Preface

Access to Colour Illustrations

Cover Illustrations

Acknowledgement

PART I: EVOLUTION OF PARASITISM AND LIFE HISTORY ADAPTATIONS

1. The Genome of Pristionchus pacificus and the Evolution of Parasitism

Introduction

Theoretical Considerations

Life-history Adaptations

P. pacificus as a Case Study

Adaptations I: Genome Evolution

Adaptations II: Nematode–Insect Interactions

Adaptations III: Evolution of Dauer Formation

Adaptations IV: Regulation of Mouth-form Dimorphism

Concluding Remarks

References

2. Life-history Plasticity and Responses to Host Defence

General Principles

Phenotypic Plasticity: Some Conceptual Issues

Helminth Life-history Trait Variation

Helminth Life-history Trait Plasticity

Analogies with Life-history Traits of Free-living Nematodes

Helminth Life-history Trait Plasticity: Inside Hosts

Evolution of Helminth Life-history Traits

Conclusion

References

3. The Complex Armoury of Plant-parasitic Nematodes

Introduction

An Exposition of Our Protagonists, and an Introduction to Some Terminology

The Molecular Basis for Parasitism by PPN

Conclusions

References

4. Innate Immunity in Caenorhabditis elegans and Other Nematodes

Introduction

The life Cycle and Natural Habitat of Six Nematode Species

Immune Response in C. elegans

Comparative Analysis of Nematode Innate Immune Systems

Conclusions

Acknowledgements

Note Added in Proof

References

PART II: MODULATION OF THE IMMUNE RESPONSE: BENEFITS FOR PARASITE AND HOST

5. Nematodes and Regulatory T cells

Introduction

Regulatory T Cells

Role of Regulatory T Cells in Mouse Models of Filarial Infection

Regulatory T cells in Intestinal Nematode Infections: The Case of Heligmosomoides polygyrus

Tregs in Other Mouse Intestinal Nematodes

Role of Tr1 and IL-10 in Nematode Infections

Natural (Thymic) or Adaptive (Induced) Tregs?

Evidence of Regulatory T Cells in Human Filarial Nematode Infection

Tregs in Human Intestinal Nematode Infections

Role of Regulatory IL-10 in Human Infections

Induction of Regulatory T Cells

Regulatory T Cell Therapy: The Future?

Acknowledgement

References

6. The Alternatively Activated Macrophage

Introduction

Macrophages in Nematode Infection

Macrophages, Th2 Immunity and Metabolism

Macrophages as Effector Cells

Macrophages, Tissue Repair and Homeostasis

Summary

Acknowledgements

References

7. Regulation of Immunity and Inflammation Following Intestinal Helminth Infection

Introduction

Gastrointestinal Nematodes

Innate Immunity to Nematodes: New Mechanisms and Novel Cell Types

Immuno-regulation During GI Nematode Infection

Beyond Th2 Responses

Effector Mechanisms of Nematode Clearance from the GI Tract

Summary

Acknowledgements

Note Added in Proof

References

8. Influence of Nematodes on Mycobacterium tuberculosis and Related Mycobacteriae: From Disease Outcome to Immune Responses

Introduction

Nematode-induced Immunoregulation

Population-based Assessments of Nematode/Mycobacterial Co-infections

In vitro Responses to PPD/Mtb/BCG in Nematode Infections

Nematode Modulation of Immune Responses in Mycobacterial Infections

Mechanisms Underlying the Regulation of Mycobacteria-specific Responses by Nematodes

Summary

References

9. Modulation of Autoimmune and Allergic Responses by Defined Nematode Molecules

Introduction

Evidence that Parasitic Nematodes Can Protect Humans from Allergy and Autoimmunity

Evidence from Animal Studies

How Are Nematodes Protective?

Identity of Molecules Involved in Immunomodulation in Animal Models and Their Mechanism of Action

Concluding Remarks

References

PART III: GENETICS DIVERSITY - HOST VERSUS PARASITE

10. Genetics and Mechanisms of Drug Resistance in Nematodes

Introduction

Mechanisms of Action of Major Anthelmintic Classes

Changes in Drug Receptors That Can Lead to Anthelmintic Resistance

ABC Transporters and Anthelmintic Resistance in Nematodes

Prospect for Developing Strategies to Increase ML Activity and Reduce Resistance by Using ABC Transporter Inhibitors

Conclusions

References

11. Genetics of Resistance to Hookworm Infection

Introduction

Evidence for Genetic Control of Human Hookworm Burden

Evidence from Animal Models

Gene Identification Studies

Do Mouse Models Inform Our Understanding of Human Infection?

Genetic Control of Co-infection?

Concluding Remarks

Acknowledgements

References

PART IV: FIGHTING BACK - THERAPEUTICS, VACCINES

12. Vaccination Against Filarial Nematodes

Introduction

The Significance of a Vaccine

Immunologic Support for Vaccines and Synergy with Chemotherapy

Protective Immunity

The Ov and LF Vaccine Molecules

Can Vaccines Against Ov and LF be Developed?

A Proposed Dual Rodent Vaccine Model

The Choice of Adjuvants for Filarial Vaccines

The Opportunities and Challenges

Concluding Remarks

References

13. A Vaccine Against Haemonchus contortus: Current Status and Future Possibilities

Introduction

The Major Vaccine Candidates and Blood Meal Digestion

Vaccination Against Haemonchus: General Considerations

Proteases Targeted as Vaccine Candidates

Protein Conformation and Protection?

Glycan and Protection?

Expression of H. contortus Proteins in C. elegans

RNA Interference: The Potential for Screening for Important Vaccine Targets

Concluding Remarks

References

14. Nematodes and Human Therapeutic Trials

Autoimmunity in a World without Helminths

Animal Models of Protection and Treatment

Mechanisms of Protection

Communication Between Helminths and Mucosal Immunity

Persistence of Protection

Clinical Trials of Helminth Therapy

Conclusion

References

PART V: NEMATODE SPECIALITIES

15. Nematode Neuropeptide Communication Systems

Introduction

Insulin-like Peptides

INS Receptors

INS Function

Neuropeptide-like Proteins

NLP Receptors

NLP Function

FMRFamide-like Peptides

FLP Expression

FLP Receptors

FLP Function and Pharmacology

Concluding Remarks

References

16. The Wolbachia Bacterial Endosymbionts of Filarial Nematodes

Introduction

Wolbachia Symbiotic Relationships

Antibiotic Treatment of Filarial Nematodes

Wolbachia as an Activator of Immunity and Driver of Disease Pathogenesis

Genomic Clues to the Molecular Interactions between Wolbachia and Filarial Nematodes

Concluding Remarks

Acknowledgements

References

17. The Nematode Cuticle: Synthesis, Modification and Turnover

Introduction

The Cuticle

Modifications that Occur in the Endoplasmic Reticulum

Modifications that Occur Outside the Endoplasmic Reticulum

The Enzymology of the Moulting Process

The Surface Coat

Concluding Remarks

Acknowledgements

References

18. Proteases of Nematodes: From Free-living to Parasite

Introduction

Metalloproteases

Serine Proteases

Aspartic Proteases

Cysteine Proteases

Concluding Remarks

Acknowledgements

References

19. Nematode Allergens

Introduction

Characterized Nematode Allergens

Nematodes and Allergy: the Two Sides of the Coin

Alternate Activities of Nematode Allergens

Conclusion

References

20. The Unusual Lipid-binding Proteins of Nematodes: NPAs, nemFABPs and FARs

Introduction

The Nematode Polyprotein Antigens/Allergens (NPAs): History

The Nematode Polyprotein Antigens/Allergens (NPAs): Structures

The Nematode FABPs (nemFABPs): History

The Nematode FABPs (nemFABPs): Structure

The Nematode Fatty Acid- and Retinol-binding Proteins (FARs): History

The Nematode Fatty Acid- and Retinol-binding Proteins (FARs): Structures

Concluding Remarks

Acknowledgements

References

Index

A

B

C

D

E

F

G

H

I

L

M

N

O

P

Q

R

S

T

U

V

W

X