Graduate Group Affiliations
3800 Spruce Street
School of Veterinary Medicine
Philadelphia, PA 19104
School of Veterinary Medicine
Philadelphia, PA 19104
Description of Research ExpertiseRESEARCH FOCUS
The studies of my lab focus on basic and applied aspects of the fish immune system. Moreover, as teleost fish represent the most ancient living bony species with an immunoglobulin-based adaptive immune system, we use these species to study key aspects of the evolution of adaptive immunity.
Our main animal model is Rainbow trout. While earlier work focused on investigating the structure, function and evolution of fish complement (see below refs# 1-7), during the last 7 years our studies have mainly focused on B cells and mucosal immunity aspects of teleost fish.
In 2006 we reported for the first time that primary B cells from a vertebrate animal (a teleost fish) contained potent phagocytic and bactericidal capacities (Fig. 1 and ref# 6). This signified a paradigm shift since B cells were not recognized as professional phagocytes at that point. Later in 2012 we found for the first time subsets of mammalian B-1 B cells with phagocytic and bactericidal capacities (Fig. 2 and ref# 17). Critically, these cells were able to present particulate antigen to CD4+ T cells.
Another primary interest of our lab is the study of fish mucosal immune responses. In 2010 we reported the first mucosal immunoglobulin (IgT) in the gut of a teleost fish (Fig. 3, ref# 17). In this study, IgT exemplified the most ancient mucosal immunoglobulin found in a vertebrate species. Thus, this finding represented a paradigm shift as the dogma at that time dictated that mucosal immunoglobulins had evolved first in tetrapod species. Later in 2013 we showed that IgT comprised the main immunoglobulin in the mucosa of the fish skin, thus supporting further the concept that IgT is a mucosal immunoglobulin (ref# 28). Both in the gut and the skin we have shown that IgT is the main immunoglobulin responding to mucosal pathogens (refs# 17 and 28). Conversely, we have demonstrated that IgM-specific responses are predominantly found in the serum of the same animals. Thus, teleost fish generate compartmentalized immunoglobulin responses against pathogens: while IgT plays a key role in mucosal areas, IgM is the principal immunoglobulin responding in systemic immunity. Critically, we have also found that IgT is the main immunoglobulin coating the microbiota of the fish gut and skin (refs# 17 and 28), similar to the immune exclusion role of IgA in mammals. Thus, a strong interest of our lab is to understand the regulation of fish microbiota by IgT, as well as to ascertain the role of microbiota in modulating fish immunity.
Our findings on IgT mucosal responses are not only of interest at the basic level but have important implications for the way that fish vaccines will be designed and tested, as a large number of fish pathogens enter through the skin and gut mucosal areas (ref# 19 and 29). In that regard, our laboratory is currently assessing the induction of IgT immune and protective responses upon vaccination through different routes (i.e., oral, bath, injection). Moreover, we are also developing immunostimulants that stimulate strong immune and protective mucosal immunity in farmed fish.
In addition to the above mentioned projects, we are currently analyzing the interactions of the different rainbow trout B cell subsets with T cells. To this end, we have recently generated mAb antibodies against rainbow trout CD4-1 and CD4-2 molecules. These mAbs have enabled us to identify and functionally characterize subpopulations of CD4-T cells in this species (manuscript in preparation). We are interested in assessing B-T cell interactions in mucosal and systemic lymphoid organs of rainbow trout, including the ability of trout APCs (i.e., phagocytic B cells, macrophages) in presenting antigen to the different subsets of systemic and mucosal trout CD4-T cells. Understanding B-T cell interactions will be crucial for the future design of more effective fish vaccines and immunostimulants.
From an evolutionary perspective, our studies are relevant to deciphering unresolved paradigms of the mammalian immune system, and thus, we are using rainbow trout as a model to address several aspects of mammalian phagocytic B cells and mucosal immunity (ref# 24).
It is important to mention that the antibodies generated in our lab that have already been reported in peer-reviewed journals, are being freely shared and distributed to other research groups. See below (DISTRIBUTION AND SHARING OF ANTIBODIES GENERATED BY OUR LAB) for the availability of antibody reagents and how to obtain them.
1. Boshra, H., J. Li, R. Peters, J. Hansen, A. Matlapudi, and J. O. Sunyer. 2004. Cloning, expression, cellular distribution and role in chemotaxis of a C5a receptor in rainbow trout: The first identification of a C5a receptor in a non-mammalian species. J. Immunol. 172:4381-90.
2. Boshra, H., A. Gelman, and J. O. Sunyer. 2004. 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.
3. Li, J., R. Peters, S. LaPatra, M. Vazzana, and J. O. Sunyer. 2004. Anaphylatoxin-like molecules generated during complement activation induce a dramatic enhancement of particle uptake in rainbow trout phagocytes. Dev. Comp. Immunol. 28:1005-21.
4. Boshra, H.., R. Peters, J. Li, and J. O. Sunyer. 2004. Production of recombinant C5a from rainbow trout (Oncorhynchus mykiss): Role in leukocyte chemotaxis and respiratory burst. Fish & Shellfish Immunol. 17:293-303.
5. Wang, L., J. O. Sunyer, L. J. Bello. 2005. Immunogenicity of a bovine viral diarrhea virus E2-C3d fusion protein containing a bovine homolog of C3d. Dev. Comp. Immunol. 29:907-15.
6. Boshra, H., T. Wang, L. Hove-Madsen, J. Hansen, J. Li, A. Matlapudi, C. J. Secombes, L. Tort, and J. O. Sunyer. 2005. Characterization of a C3a receptor in rainbow trout and Xenopus: the first identification of C3a receptors in nonmammalian species. J. Immunol. 175:2427-37.
7. Li, J., H. Boshra, and J. O. Sunyer. 2005. Evolution of anaphylatoxins, their diversity and novel roles in innate in immunity: Insights from the study of fish complement. Veterinary Immunol. Immunopathol. 108: 77-89.
8. Li, J., D. R. Barreda, Y. A. Zhang, H. Boshra, A. E. Gelman, S. LaPatra, L. Tort, and J. O. Sunyer. 2006. B lymphocytes from early vertebrates have potent phagocytic and microbicidal abilities. Nat. Immunol. 7:1116-1124.
9. Lovoll, M., T. Kilvik, H. Boshra, J. Bogwald, J. O. Sunyer, and R. A. Dalmo. 2006. Maternal transfer of complement components C3-1, C3-3, C3-4, C4, C5, C7, Bf, and Df to offspring in rainbow trout (Oncorhynchus mykiss). Immunogenetics .58:168-179.*
10. Boshra, H., J. Li, and J. O. Sunyer. 2006. Recent advances on the complement system of Teleost Fish: Novel components and new functions. Fish & Shellfish Immunol. 20 (2): 239-262.
11. Gelman, A. E., D. F. LaRosa, J. Zhang, P. T. Walsh, Y. Choi, J. O. Sunyer, and L. A. Turka. 2006. The adaptor molecule MyD88 activates PI-3 kinase signaling in CD4+ T cells and enables CpG oligodeoxynucleotide-mediated costimulation. Immunity. 25:783-793.
12. Løvoll M, Johnsen H, Boshra H, Bøgwald J, J. O. Sunyer and R. A. Dalmo. 2007. The ontogeny and extrahepatic expression of complement factor C3 in Atlantic salmon (Salmo salar). Fish & Shellfish Immunol. 23:542-552.
13. Hodawadekar, S., D. Yu, D. Cozma, B. Freedman, J. O. Sunyer, M. L. Atchinson, and Thomas-Tikhonenko A. 2007. B-Lymphoma cells with epigenetic silencing of Pax5 trans-differentiate into macrophages, but not other hematopoietic lineages. Exp Cell Res. 15:331-40.
14. McCarthy, S. E., R. F. Johnson, Y. A. Zhang, J. O. Sunyer, and R. N. Harty. 2007. Role for amino acids 212KLR214 of Ebola virus VP40 in assembly and budding. J. Virol. 81:11452-11460.
15. Zhang, Y. A., J. Hikima, J. Li, S. E. LaPatra, Y. P. Luo, and J. O. Sunyer. 2009. Conservation of structural and functional features in a primordial CD80/86 molecule from rainbow trout (Oncorhynchus mykiss), a primitive teleost fish. J. Immunol. 183:83-96.
16. Liu, Y., L. Cocka, A. Okumura, Y. A. Zhang, J. O. Sunyer, and R. N. Harty. 2010. Conserved motifs within Ebola and Marburg virus VP40 proteins are important for stability, localization, and subsequent budding of virus-like particles. J. Virol. 84:2294-2303.
17. Zhang, Y. A., I. Salinas, J. Li, D. Parra, S. Bjork, Z. Xu, S. E. LaPatra, J. Bartholomew, and J. O. Sunyer. 2010. IgT, a primitive immunoglobulin class specialized in mucosal immunity. Nat. Immunol. 11:827-835.
18. Zhang, Y.A., Salinas, I., and J. O. Sunyer. 2011. Recent findings on the structure and function of teleost IgT. Fish & Shellfish Immunol. 31:627-34.
19. Salinas, I., Zhang, Y.A., and J. O. Sunyer. 2011. Mucosal immunoglobulins and B cells of teleost fish. Dev. Comp. Immunol. 35:1346-65.
20. Parra, D., A. M. Rieger, J. Li, Y.A. Zhang, L. M. Randall, C.A. Hunter, D. R. Barreda and J. O. Sunyer. 2012. Pivotal Advance: Peritoneal cavity B-1 B cells have phagocytic and microbicidal capacities, and present phagocytosed antigen to CD4+ T cells. J. Leuk. Biol. 91(4):526-36.
21. Rowley, A.F., Morgan, E.L., Taylor, G.W., Sunyer, J.O., Holland, J.W., Vogan C,L., C.J. Secombes. 2012. Interaction between eicosanoids and the complement system in salmonid fish. Dev. Comp. Immunol. 36:1-9.
22. J. O. Sunyer. 2012. Evolutionary and Functional Relationships of B Cells from Fish and Mammals: Insights into Their Novel Roles in Phagocytosis and Presentation of Particulate Antigen. Infect. Disor.-Drug Targ. 12:200-12.
23. Ordas, M.C., B. Dixon, J. O. Sunyer, S. Bjork, J. Barholomew, T. Korytar, T., B. koller, A. Cuesta, C. Tafalla. 2012. Identification of a novel CCR7 gene in rainbow trout with differential expression in the context of mucosal or systemic infection. Dev Comp Immunol. 38:302-11.
24. J. O. Sunyer. 2013. Perspective article: Fishing for new paradigms in teleost fish immune systems. Nat. Immunol. 14:320-6.
25. Parra, D., Takizawa F. & J. O. Sunyer. 2013. Evolution of B-cell Immunity. Ann. Rev. Ani. Vet. Biosc. 1:65-97.
26. Castro, R., L. Jouneau, H.P. Pham, O. Bouchez, V. Giudicelli, M-P. Lefranc, E. Quillet, A. Benmansour, A. Six, S. Fillatreau, O. Sunyer, P. Boudinot. 2013. Teleost fish mount complex clonal IgM and IgT responses in spleen upon systemic viral infection. PLoS Pathog. 2013 Jan;9(1):e1003098. doi: 10.1371/journal.ppat.1003098. Epub 2013 Jan 10.
27. S. Fillatreau, A. Six, S.Magadan, R. Castro, J. O. Sunyer, P. Boudinot. 2013. The astonishing diversity of Ig classes and B cell repertoires in teleost fish. Front. Immunol. 2013;4:28. doi: 10.3389/fimmu.2013.00028. Epub 2013 Feb 13.
28. Xu, Z., Parra, D., Gomez, D., Salinas, I., Zhang, Y.A., Jørgensen G.L., Skjødt, K., Rasmussen, K.J.,Buchmann K., LaPatra, S.L., J. O. Sunyer. 2013. Teleost skin, an ancient mucosal surface that elicits gut-like immune-responses. Proc. Natl. Acad. Sci. U S A.110:13097-13102.
29. Gomez, D., Sunyer, J.O., Salinas, I. The mucosal immune system of fish: the evolution of tolerating commensals while fighting pathogens. 2013. Fish & Shellfish Immunol. 35:1729-39.
30. Gomez, D., Bartholomew, J., Sunyer, J.O. 2014. Biology and mucosal immunity to myxozoans. Dev. Comp. Immunol. 43:243-56.
31. Bjork, S.J., Zhang, Y.A., Hurst, C.N., Alonso-Naveiro, M.E., Alexander, J.D., Sunyer, J.O., Bartholomew, J.L. 2014. Defenses of susceptible and resistant Chinook salmon (Onchorhynchus tshawytscha) against the myxozoan parasite Ceratomyxa shasta. Fish & Shellfish Immunol. 37:87-95.
32. Wu, N., LaPatra, S.E., Li, J., Sunyer, J.O**., Zhang, Y.A. 2014. Complement C5a acts as molecular adjuvant in fish by enhancing antibody response to soluble antigen. Fish & Shellfish Immunol.40:616-23.
33. Reyes-Cerpa, S., Reyes-López, F., Toro-Ascuy, D., Montero, R., Maisey, K., Acuña-Castillo, C., Sunyer, J.O., Parra, D., Sandino, A.M., Imarai, M. 2014. Induction of anti-inflammatory cytokine expression by IPNV in persistent infection. Fish & Shellfish Immunol. 41:172-182.
*Dr. Sunyer and Dr. Dalmo are equal corresponding authors for manuscript # 12.
** Dr. Sunyer and Dr. Zhang are equal corresponding authors for manuscript# 32.
Selected PublicationsWang, 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. Page: (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.