Abstract
Proliferative kidney disease (PKD) is a parasitic infection of salmonid fish characterized by hyper-secretion of immunoglobulins in response to the presence of the myxozoan parasite, Tetracapsuloides bryosalmonae. In this context, we hypothesized that the BAFF/APRIL axis, known to play a major role in B cell differentiation and survival in mammals, could be affected by the parasite and consequently be involved in the apparent shift in normal B cell activity. To regulate B cell activity, BAFF and APRIL bind to transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and B cell maturation antigen (BCMA), whereas BAFF also binds to BAFF receptor (BAFF-R). In teleost fish, although some BAFF and APRIL sequences have been reported, their receptors have not been identified. Thus, as a first step in the current work, we have identified homologues to mammalian TACI, BCMA and BAFF-R in rainbow trout (Oncorhynchus mykiss), that constitute the first report of BAFF and APRIL receptor sequences in fish. Subsequently we studied the transcriptional modulation of BAFF, APRIL, and the fish-specific related cytokine, BALM and their putative receptors in fish naturally exposed to T. bryosalmonae. Finally, to gain further insights on the functional role that these cytokines play during the course of PKD, we have studied their effect on the survival of kidney IgM+ B cells and on immunoglobulin transcription. Our results support the premise that the BAFF / APRIL axis could play an important role during PKD, which may open the possibility of new therapeutic treatments against the disease.
Original language | English |
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Article number | 0174249 |
Number of pages | 24 |
Journal | PloS ONE |
Volume | 12 |
Issue number | 3 |
DOIs | |
Publication status | Published - 21 Mar 2017 |
Bibliographical note
We would like to thank Lucia González for technical assistance and Rosario Castro for producing some of the cDNAs used in this study. This work was supported by the European Research Council (ERC Starting Grant 2011 280469) and by the European Commission under the 7th Framework Programme for Research and Technological Development (FP7) of the European Union (Grant Agreement 311993 TARGETFISH) and under the Horizon H2020 research and innovation programme (Grant H2020-634429 ParaFishControl). This work was also partially funded by project AGL2014-54456-JIN from the Spanish Ministry of Economy and Competitiveness (MINECO). JWH was supported by the Swiss National Science Foundation (grant reference CRSII3_147649-1).Keywords
- B-LYMPHOCYTE STIMULATOR
- CELL ACTIVATING FACTOR
- TNF RECEPTOR
- ONCORHYNCHUS-MYKISS
- MOLECULAR-STRUCTURE
- FUNCTIONAL-ANALYSIS
- EXPRESSION ANALYSIS
- CARTILAGINOUS FISH
- IMMUNE-RESPONSE
- SALMO-GAIRDNERI