Professor, Immunology/Pathobiology, University of Pennsylvania School of Veterinary Medicine

Research Areas: Fish immunology, Innate immunity, Immunology,
PubMed Link
Contact Information:
3800 Spruce Street School of Veterinary Medicine
 Email sunyer@vet.upenn.edu

My laboratory is interested in understanding the role of the complement system of teleost fish in innate and adaptive immunity. We are also committed to elucidating the evolutionary history of the components, molecular pathways and cells involved in these ancient immune processes. Teleost fish are the first, and thus far, the only living organisms from which multiple forms of functionally active C3 have been isolated and characterized. In the rainbow trout (our fish model) three C3 isoforms (C3-1, C3-3, and C3-4) have been characterized. The most important feature of the three trout C3 isoforms lies in their differences in binding to several complement-activating surfaces. It has been hypothesized that this unique structural and functional diversity in C3 may provide a mechanism for recognizing a broader range of microorganisms, thereby allowing fish to expand their innate immune recognition capabilities. One of our long term objectives is to understand the significance of this C3 diversity in fish immune processes. Complement plays an important role in the development of an inflammatory response. In this regard C3a and C5a anaphylatoxins generated during the activation of C3 and C5 components are key effectors in inflammation. These molecules are considered to be endogenous danger signals that, in addition to inducing the development of an inflammatory response, trigger the activation of several key innate immune processes. Thus far we have generated pure forms of trout C3a-1, C3a-3, C3a-4 and C5a anaphylatoxins, characterized some of their functions, and identified and cloned their receptors, including C3aR and C5aR. These studies represent the first characterization of anaphylatoxins and their receptors in a non-mammalian species. The study of these ancient Amolecules in this teleost fish has revealed not only conserved structural domains and biological roles, but also unique features related to key structural elements and novel functions not seen in mammals.

A strong interest of our group is to apply some of the knowledge derived from the study of these immune processes in fish towards the development of molecular adjuvants to be used as part of fish vaccines. To this end, we are currently studying the involvement of some trout complement molecules, including C3d and C5a, in enhancing antibody responses against selected antigens and fish pathogens.

Wang, L., Sunyer, J.O., Bello, L.J. Fusion to C3d enhances the immunogenicity of the E2 glycoprotein of type 2 bovine viral diarrhea virus. J. Virol. 78: 1616-22, 2004.

Rotllant, J., Parra, D., Peters, R., Boshra, Sunyer, J.O. Generation, purification and functional characterization of three C3a anaphylatoxins in rainbow trout: Role in leukocyte chemotaxis and respiratory burst. Dev. Comp. Immunol. 28: 815-28, 2004.

Boshra, H., Li J., Peters R., Hansen J., Matlapudi A., Sunyer J.O. Cloning, expression, cellular distribution and role in chemotaxis of a C5aR rainbow trout: The first identification of a C5aR in a non-mammalian species. J. Immunol. 172: 4381-90, 2004.

Boshra, H., Gelman, A., Sunyer, J.O. Structural and functional characterization of complement C4 and C1s-like molecules in teleost fish: Insights into the evolution of classical and alternative pathways. J. Immunol. 173: 349-59, 2004.

Li, J., Peters, R., Lapatra, S., Vazzana, M., Sunyer, J.O. Anaphylatoxin-like molecules generated during complement activation induce a dramatic enhancement of particle uptake in rainbow trout phagocytes. Dev. Comp. Immunol. : (In press), 2004.

Boshra, H , Peters, R., Li, J., Sunyer, J.O. Production of recombinant C5a from rainbow trout (Oncorhynchus mykiss): Role in leukocyte chemotaxis and respiratory burst. Fish & Shellfish Immunol. : (In press), 2004.

Sunyer, J. O., Boshra, H., Lorenzo, G., Parra, D., Freedman, B., Bosch, N. Evolution of the complement as an effector system in innate and adaptive immunity. Immunol. Research 27: 1-16, 2003.