CK9 is a rainbow trout (Oncorhynchus mykiss) CC chemokine phylogenetically related to mammalian CCL25. Although CK9 is known to be transcriptionally regulated in response to inflammation particularly in mucosal tissues, its functionality has never been revealed. In the current work, we have demonstrated that CK9 is chemoattractant for antigen presenting cells (APCs) expressing major histocompatibility complex class II (MHC II) on the cell surface. Among these APCs, CK9 has a strong chemotactic capacity for both B cells (IgM+ and IgT+) and macrophages. Along with its chemotactic capacities, CK9 modulated the MHC II turnover of B lymphocytes and up-regulated the phagocytic capacity of both IgM+ cells and macrophages. Although CK9 had no lymphoproliferative effects, it increased the survival of IgT+ lymphocytes. Furthermore, we have established that the chemoattractant capacity of CK9 is strongly increased after pre-incubation of leukocytes with a T-independent antigen, whereas B cell receptor (BCR) cross-linking strongly abrogated their capacity to migrate to CK9, indicating that CK9 preferentially attracts B cells at the steady state or under BCR-independent stimulation. These results point to CK9 being a key regulator of B lymphocyte trafficking in rainbow trout, able to modulate innate functions of teleost B lymphocytes and macrophages.
There are still many details of how intestinal immunity is regulated that remain unsolved in teleost. Although leukocytes are present all along the digestive tract, most immunological studies have focused on the posterior segments and the importance of each gut segment in terms of immunity has barely been addressed. In the current work, we have studied the regulation of several immune genes along five segments of the rainbow trout (Oncorhynchus mykiss) digestive tract, comparing the effects observed in response to an infectious pancreatic necrosis virus (IPNV) infection to those elicited by oral vaccination with a plasmid coding for viral VP2. We have focused on the regulation of several mucosal chemokines, chemokine receptors, the major histocompatibility complex II (MHC-II) and tumor necrosis factor α (TNF-α). Furthermore, the recruitment of IgM(+) cells and CD3(+) cells was evaluated along the different segments in response to IPNV by immunohistochemical techniques. Our results provide evidences that there is a differential regulation of these immune genes in response to both stimuli along the gut segments. Along with this chemokine and chemokine receptor induction, IPNV provoked a mobilization of IgM(+) and IgT(+) cells to the foregut and pyloric caeca region, and CD3(+) cells to the pyloric caeca and midgut/hindgut regions. Our results will contribute to a better understanding of how mucosal immunity is orchestrated in the different gut segments of teleost.
CK11 is a rainbow trout (Oncorhynchus mykiss) CC chemokine phylogenetically related to both mammalian CCL27 and CCL28 chemokines, strongly transcribed in skin and gills in homeostasis, for which an immune role had not been reported to date. In the current study, we have demonstrated that CK11 is not chemotactic for unstimulated leukocyte populations from central immune organs or mucosal tissues but instead exerts a potent antimicrobial activity against a wide range of rainbow trout pathogens. Our results show that CK11 strongly inhibits the growth of different rainbow trout Gram-positive and Gram-negative bacteria, namely Lactococcus garvieae, Aeromonas salmonicida subsp. salmonicida, and Yersinia ruckeri and a parasitic ciliate Ichthyophthirius multifiliis. Similarly to mammalian chemokines and antimicrobial peptides, CK11 exerted its antimicrobial activity, rapidly inducing membrane permeability in the target pathogens. Further transcriptional studies confirmed the regulation of CK11 transcription in response to exposure to some of these pathogens in specific conditions. Altogether, our studies related to phylogenetic relations, tissue distribution, and biological activity point to CK11 as a potential common ancestor of mammalian CCL27 and CCL28. To our knowledge, this study constitutes the first report of a fish chemokine with antimicrobial activity, thus establishing a novel role for teleost chemokines in antimicrobial immunity that supports an evolutionary relationship between chemokines and antimicrobial peptides.
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