[Frontiers in Bioscience 14, 2051-2088, January 1, 2009]

The role of saliva in tick feeding

Ivo M.B Francischetti1, Anderson Sa-Nunes1, Ben J. Mans1, Isabel M. Santos2, Jose M.C. Ribeiro1

1Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, Bethesda MD, USA,2 Department of Biochemistry and Immunology, Ribeirao Preto School of Medicine, Ribeirao Preto, SP, Brazil

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Problems ticks face when taking a blood meal
3.1. Platelets
3.2. The blood coagulation cascade and its regulation
3.2.1. Initiation
3.2.2. Amplification
3.2.3. Blood-borne tissue factor and microparticles
3.2.4. Tissue factor and inflammation
3.2.5. The 'contact' pathway
3.2.6. Endogenous anticoagulant regulators of the clotting cascade
3.2.7. Fibrinolytic system
3.3. Angiogenesis and wound healing
3.4. Ticks and immunity: an overview
3.4.1. Mast cells
3.4.2. Eosinophils
3.4.3. Dendritic cells
3.4.4. Macrophages
3.4.5. Neutrophils
3.4.6. Basophils
3.4.7. T lymphocytes
3.4.8. B lymphocytes
3.4.9. Molecular communication between the different cell types: complement, cytokines and chemotactic factors
3.4.10. Cytokines, pain, and itching responses
4. Toward the tick sialoverse
4.1. Glycine-rich, or proline-rich, collagen-like superfamily
4.2. Mucins
4.3. Antigen 5 (AG5) protein family
4.4. Ixodegrin superfamily
4.5. Ixostatins
4.6. Families containing protease inhibitor domains
4.6.1. Kunitz domain containing proteins
4.6.2. Serpin domain family
4.6.3. Cystatins
4.6.4. Thyropin family
4.6.5. TIL domain-containing peptides
4.6.6. Hirudin-like/madanin/variegin superfamily
4.6.7. Basic tail and 18.3-kDa superfamily
4.6.8. Carboxypeptidase inhibitor family
4.7. Lipocalins
4.8. 8.9-kDa polypeptide family
4.9. 23-kDa family
4.10. 13-kDa family
4.11. 12-kDa family
4.12. PGFG repeat family
4.13. IS4 family
4.14. Cytotoxin-like family
4.15. 16-kDa family
4.16. Enzymes
4.17. Immunity-related products
4.17.1. Pattern recognition proteins
4.17.1.1. Ficolins/Ixoderins
4.17.1.2. Peptidoglycan recognition proteins
4.17.1.3. Galactose-binding protein
4.17.1.4. ML domain containing proteins
4.17.2. Thioester / alpha 2 macroglobulin family
4.17.3. Antimicrobial peptides and proteins
4.17.3.1. Lysozyme
4.17.3.2. Defensins
4.17.3.3. Microplusin family and other histidine-rich peptides
4.17.3.4. 5.3-kDa family
4.17.3.5. Y-rich GR peptide family
4.18. Metastriate-specific families
4.19. Prostriate-specific families
4.20. Argasidae-specific families
4.21. Secreted conserved proteins
4.22. Possible housekeeping proteins
4.23. Non-peptidic salivary components
4.24. Evolutionary considerations
5. Conclusions and perspectives
6. Acknowledgments
7. References

1. ABSTRACT

When attempting to feed on their hosts, ticks face the problem of host hemostasis (the vertebrate mechanisms that prevent blood loss), inflammation (that can produce itching or pain and thus initiate defensive behavior on their hosts) and adaptive immunity (by way of both cellular and humoral responses). Against these barriers, ticks evolved a complex and sophisticated pharmacological armamentarium, consisting of bioactive lipids and proteins, to assist blood feeding. Recent progress in transcriptome research has uncovered that hard ticks have hundreds of different proteins expressed in their salivary glands, the majority of which have no known function, and include many novel protein families (e.g., their primary structure is unique to ticks). This review will address the vertebrate mechanisms of these barriers as a guide to identify the possible targets of these large numbers of known salivary proteins with unknown function. We additionally provide a supplemental Table that catalogues over 3,500 putative salivary proteins from various tick species, which might assist the scientific community in the process of functional identification of these unique proteins. This supplemental file is accessble fromhttp://exon.niaid.nih.gov/transcriptome/tick_review/Sup-Table-1.xls.gz.