Fishes are the phylogenetically oldest vertebrate group, which includes more than one-half of the vertebrates on the planet; additionally, many species have ecological and economic importance. Fish are the first evolved group of organisms with adaptive immune mechanisms; consequently, they are an important link in the evolution of the immune system, thus a potential model for understanding the mechanisms of immunoregulation. Currently, the influence of the neurotransmitter acetylcholine (ACh) on the cells of the immune system is widely studied in mammalian models, which have provided evidence on ACh production by immune cells (the noncholinergic neuronal system); however, these neuroimmunomodulation mechanisms in fish and lower vertebrates are poorly studied. Therefore, the objective of this review paper was to analyze the influence of the cholinergic system on the immune response of teleost fish, which could provide information concerning the possibility of bidirectional communication between the nervous and immune systems in these organisms and provide data for a better understanding of basic issues in neuroimmunology in lower vertebrates, such as bony fishes. Thus, the use of fish as a model in biomedical research may contribute to a better understanding of human diseases and diseases in other animals. 1. Immune System in Teleost Fishes Fishes are the phylogenetically oldest vertebrate group and appeared >560 million years ago. This group includes >27,000 species, representing more than one half of the vertebrates on the planet. The vast majority of fishes are teleosts (teleostei, possessing a bony skeleton) and some are noted for their ecological and economic importance, whereas other species are widely used as biological models for genomic studies and developmental biology [1, 2]. In addition, because these organisms are the first that present adaptive immune mechanisms (Figure 1), the Big Bang of Immunology [3], the study of the immune system of these organisms is of great relevance because it provides information on the evolution of the immune system in vertebrates, thus supporting the understanding of basic aspects of immunology, therefore the possible treatment of emerging diseases in humans and in other animals [4]. Figure 1: Main humoral, cellular, and anatomical components of the immune system in fishes. Fish lymphoid organs: pronephros (1), spleen (2), and thymus (3). 1.1. Lymphoid Organs Fishes, unlike mammals, lack lymph nodes and bone marrow [5]. However, the anterior kidney or pronephros, analog evolutionary of the bone marrow,
References
[1]
I. A. Hurley, R. L. Mueller, K. A. Dunn et al., “A new time-scale for ray-finned fish evolution,” Proceedings of the Royal Society B, vol. 274, no. 1609, pp. 489–498, 2007.
[2]
J.-N. Volff, “Genome evolution and biodiversity in teleost fish,” Heredity, vol. 94, no. 3, pp. 280–294, 2005.
[3]
G. W. Litman, J. P. Cannon, and L. J. Dishaw, “Reconstructing immune phylogeny: new perspectives,” Nature Reviews Immunology, vol. 5, no. 11, pp. 866–879, 2005.
[4]
P. R. Rauta, B. Nayak, and S. Das, “Immune system and immune responses in fish and their role in comparative immunity study: a model for higher organisms,” Immunology Letters, vol. 148, no. 1, pp. 23–33, 2012.
[5]
C. M. Press and ？. Evensen, “The morphology of the immune system in teleost fishes,” Fish & Shellfish Immunology, vol. 9, no. 4, pp. 309–318, 1999.
[6]
P. Zwollo, S. Cole, E. Bromage, and S. Kaattari, “B cell heterogeneity in the teleost kidney: evidence for a maturation gradient from anterior to posterior kidney,” Journal of Immunology, vol. 174, no. 11, pp. 6608–6616, 2005.
[7]
A. Zapata, B. Diez, T. Cejalvo, C. Gutiérrez-De Frías, and A. Cortés, “Ontogeny of the immune system of fish,” Fish & Shellfish Immunology, vol. 20, no. 2, pp. 126–136, 2006.
[8]
A. J. Davidson and L. I. Zon, “The ‘definitive’ (and ‘primitive’) guide to zebrafish hematopoiesis,” Oncogene, vol. 23, no. 43, pp. 7233–7246, 2004.
[9]
T. J. Bowden, P. Cook, and J. H. W. M. Rombout, “Development and function of the thymus in teleosts,” Fish & Shellfish Immunology, vol. 19, no. 5, pp. 413–427, 2005.
[10]
L. Gao, C. He, X. Liu et al., “The innate immune-related genes in catfish,” International Journal of Molecular Science, vol. 13, no. 11, pp. 14172–14202, 2012.
[11]
T.-J. Chia, Y.-C. Wu, J.-Y. Chen, and S.-C. Chi, “Antimicrobial peptides (AMP) with antiviral activity against fish nodavirus,” Fish & Shellfish Immunology, vol. 28, no. 3, pp. 434–439, 2010.
[12]
S. Saurabh and P. K. Sahoo, “Lysozyme: an important defence molecule of fish innate immune system,” Aquaculture Research, vol. 39, no. 3, pp. 223–239, 2008.
[13]
C. S. F. Bah, E. F. Fang, T. B. Ng, S. Mros, M. McConnell, and A. El-Din Ahmed Bekhit, “Purification and characterization of a rhamnose-binding chinook salmon roe lectin with antiproliferative activity toward tumor cells and nitric oxide-inducing activity toward murine macrophages,” Journal of Agricultural and Food Chemistry, vol. 59, no. 10, pp. 5720–5728, 2011.
[14]
B. Gisladottir, S. Gudmundsdottir, L. Brown, Z. O. Jonsson, and B. Magnadottir, “Isolation of two C-reactive protein homologues from cod (Gadus morhua L.) serum,” Fish & Shellfish Immunology, vol. 26, no. 2, pp. 210–219, 2009.
[15]
H. Boshra, J. Li, and J. O. Sunyer, “Recent advances on the complement system of teleost fish,” Fish & Shellfish Immunology, vol. 20, no. 2, pp. 239–262, 2006.
[16]
P. Alvarez-Pellitero, “Fish immunity and parasite infections: from innate immunity to immunoprophylactic prospects,” Veterinary Immunology and Immunopathology, vol. 126, no. 3-4, pp. 171–198, 2008.
[17]
M. A. Sylvie, P. Boudinot, and E. Bengtén, “Comprehensive survey and genomic characterization of Toll-Like Receptors (TLRs) in channel catfish, Ictalurus punctatus: identification of novel fish TLRs,” Immunogenetics, vol. 65, no. 7, pp. 511–530, 2013.
[18]
A. M. Rieger and D. R. Barreda, “Antimicrobial mechanisms of fish leukocytes,” Developmental and Comparative Immunology, vol. 35, no. 12, pp. 1238–1245, 2011.
[19]
D. Pali？, J. Ostoji？, C. B. Andreasen, and J. A. Roth, “Fish cast NETs: neutrophil extracellular traps are released from fish neutrophils,” Developmental and Comparative Immunology, vol. 31, no. 8, pp. 805–816, 2007.
[20]
L. Pijanowski, L. Golbach, E. Kolaczkowska, M. Scheer, B. M. L. Verburg-van Kemenade, and M. Chadzinsk, “Carp neutrophilic granulocytes form extracellular traps via ROS-dependent and independent pathways,” Fish & Shellfish Immunology, vol. 34, no. 5, pp. 1244–1252, 2013.
[21]
I. L. Leknes, “Eosinophilic granule cells and endocytic cells in intestinal wall of pearl gouramy (Anabantidae: Teleostei),” Fish & Shellfish Immunology, vol. 23, no. 4, pp. 897–900, 2007.
[22]
A. E. Ellis, “Innate host defense mechanisms of fish against viruses and bacteria,” Developmental and Comparative Immunology, vol. 25, no. 8-9, pp. 827–839, 2001.
[23]
K. J. Laing and J. D. Hansen, “Fish T cells: recent advances through genomics,” Developmental and Comparative Immunology, vol. 35, no. 12, pp. 1282–1295, 2011.
[24]
P. Zwollo, “Dissecting teleost B cell differentiation using transcription factors,” Developmental and Comparative Immunology, vol. 35, no. 9, pp. 898–905, 2011.
[25]
M. Barr, K. Mott, and P. Zwollo, “Defining terminally differentiating B cell populations in rainbow trout immune tissues using the transcription factor XbpI,” Fish & Shellfish Immunology, vol. 31, no. 6, pp. 727–735, 2011.
[26]
J. O. Sunyer, “Fishing for mammalian paradigms in the teleost immune system,” Nature Immunology, vol. 14, pp. 320–326, 2013.
[27]
H. Dooley and M. F. Flajnik, “Antibody repertoire development in cartilaginous fish,” Developmental and Comparative Immunology, vol. 30, no. 1-2, pp. 43–56, 2006.
[28]
L. Tort, J. C. Balasch, and S. Mackenzie, “Fish immune system. A crossroads between innate and adaptive responses,” Inmunologia, vol. 22, no. 3, pp. 277–286, 2003.
[29]
R. Castro, D. Bernard, M. P. Lefranc, A. Six, A. Benmansour, and P. Boudinot, “T cell diversity and TcR repertoires in teleost fish,” Fish & Shellfish Immunology, vol. 31, no. 5, pp. 644–654, 2011.
[30]
T. Wang, B. Gorgoglione, T. Maehr et al., “Fish Suppressors of Cytokine Signaling (SOCS): gene discovery, modulation of expression and function,” Journal of Signal Transduction, vol. 2011, Article ID 905813, 20 pages, 2011.
[31]
B. M. L. Verburg-van Kemenade, C. M. S. Ribeiro, and M. Chadzinska, “Neuroendocrine-immune interaction in fish: differential regulation of phagocyte activity by neuroendocrine factors,” General and Comparative Endocrinology, vol. 172, no. 1, pp. 31–38, 2011.
[32]
F. J. Arenzana, D. Clemente, R. Sánchez-González, A. Porteros, J. Aijón, and R. Arévalo, “Development of the cholinergic system in the brain and retina of the zebrafish,” Brain Research Bulletin, vol. 66, no. 4–6, pp. 421–425, 2005.
[33]
N. C. Bols, J. L. Brubacher, R. C. Ganassin, and L. E. J. Lee, “Ecotoxicology and innate immunity in fish,” Developmental and Comparative Immunology, vol. 25, no. 8-9, pp. 853–873, 2001.
[34]
T. Galloway and R. Handy, “Immunotoxicity of organophosphorous pesticides,” Ecotoxicology, vol. 12, no. 1–4, pp. 345–363, 2003.
[35]
Y. Abreu-Villa？a, C. C. Filgueiras, and A. C. Manh？es, “Developmental aspects of the cholinergic system,” Behavioural Brain Research, vol. 221, no. 2, pp. 367–378, 2011.
[36]
I. Wessler, C. J. Kirkpatrick, and K. Racké, “The cholinergic ‘pitfall’: acetylcholine, a universal cell molecule in biological systems, including humans,” Clinical and Experimental Pharmacology and Physiology, vol. 26, no. 3, pp. 198–205, 1999.
[37]
D. Clemente, á. Porteros, E. Weruaga et al., “Cholinergic elements in the zebrafish central nervous system: histochemical and immunohistochemical analysis,” Journal of Comparative Neurology, vol. 474, no. 1, pp. 75–107, 2004.
[38]
K. Funakoshi and M. Nakano, “The sympathetic nervous system of anamniotes,” Brain, Behavior and Evolution, vol. 69, no. 2, pp. 105–113, 2007.
[39]
P. E. Phelps, R. P. Barber, and J. E. Vaughn, “Embryonic development of choline acetyltransferase in thoracic spinal motor neurons: somatic and autonomic neurons may be derived from a common cellular group,” Journal of Comparative Neurology, vol. 307, no. 1, pp. 77–86, 1991.
[40]
K. Funakoshi, Y. Atobe, T. Hisajima et al., “Choline acetyltransferase immunoreactive sympathetic ganglion cells in a teleost, Stephanolepis cirrhifer,” Autonomic Neuroscience: Basic and Clinical, vol. 99, no. 1, pp. 31–39, 2002.
[41]
I. Rodríguez-Moldes, P. Molist, F. Adrio et al., “Organization of cholinergic systems in the brain of different fish groups: a comparative analysis,” Brain Research Bulletin, vol. 57, no. 3-4, pp. 331–334, 2002.
[42]
D. Clemente, F. J. Arenzana, R. Sánchez-González, á. Porteros, J. Aijón, and R. Arévalo, “Comparative analysis of the distribution of choline acetyltransferase in the central nervous system of cyprinids,” Brain Research Bulletin, vol. 66, no. 4–6, pp. 546–549, 2005.
[43]
T. Mueller, P. Vernier, and M. F. Wullimann, “The adult central nervous cholinergic system of a neurogenetic model animal, the zebrafish Danio rerio,” Brain Research, vol. 1011, no. 2, pp. 156–169, 2004.
[44]
E. P. Rico, D. B. Rosemberg, K. J. Seibt, K. M. Capiotti, R. S. Da Silva, and C. D. Bonan, “Zebrafish neurotransmitter systems as potential pharmacological and toxicological targets,” Neurotoxicology and Teratology, vol. 33, no. 6, pp. 608–617, 2011.
[45]
S. Steele, V. Li, A. Lo, H. Cheng, and S. Perry, “The role of the M2 muscarinic receptor in the development of hypoxic bradycardia in zebrafish (Danio rerio) larvae,” Comparative Biochemistry and Physiology A, vol. 146, supplement 4, p. S182, 2007.
[46]
E. D. Levin, Z. Bencan, and D. T. Cerutti, “Anxiolytic effects of nicotine in zebrafish,” Physiology & Behavior, vol. 90, no. 1, pp. 54–58, 2007.
[47]
Z. Bencan and E. D. Levin, “The role of α7 and α4β2 nicotinic receptors in the nicotine-induced anxiolytic effect in zebrafish,” Physiology & Behavior, vol. 95, no. 3, pp. 408–412, 2008.
[48]
C. R. Dias Assis, A. Guedes Linhares, V. M. Oliveira et al., “Comparative effect of pesticides on brain acetylcholinesterase in tropical fish,” Science of the Total Environment, vol. 441, pp. 141–150, 2012.
[49]
B. M. L. Verburg-Van Kemenade, E. H. Stolte, J. R. Metz, and M. Chadzinska, “Neuroendocrine-immune interactions in teleost fish,” in Fish Physiology, S. D. McCormick, A. P. Farrell, and C. J. Brauner, Eds., vol. 28, chapter 7, pp. 313–364, 2009.
[50]
A. S. Balasubramanian and C. D. Bhanumathy, “Noncholinergic functions of cholinesterases,” FASEB Journal, vol. 7, no. 14, pp. 1354–1358, 1993.
[51]
E. Weitnauer, A. Robitzki, and P. G. Layer, “Aryl acylamidase activity exhibited by butyrylcholinesterase is higher in chick than in horse, but much lower than in fetal calf serum,” Neuroscience Letters, vol. 254, no. 3, pp. 153–156, 1998.
[52]
L. Pezzementi and A. Chatonnet, “Evolution of cholinesterases in the animal kingdom,” Chemico-Biological Interactions, vol. 187, no. 1–3, pp. 27–33, 2010.
[53]
F. Ferriere, N. A. Khan, J.-P. Meyniel, and P. Deschaux, “Characterisation of serotonin transport mechanisms in rainbow trout peripheral blood lymphocytes: role in PHA-induced lymphoproliferation,” Developmental and Comparative Immunology, vol. 23, no. 1, pp. 37–50, 1999.
[54]
C. M. Flory, “Phylogeny of neuroimmunoregulation: effects of adrenergic and cholinergic agents on the in vitro antibody response of the rainbow trout, Onchorynchus mykiss,” Developmental and Comparative Immunology, vol. 14, no. 3, pp. 283–294, 1990.
[55]
C. M. Flory and C. J. Bayne, “The influence of adrenergic and cholinergic agents on the chemiluminescent and mitogenic responses of leukocytes from the rainbow trout, Oncorhynchus mykiss,” Developmental and Comparative Immunology, vol. 15, no. 3, pp. 135–142, 1991.
[56]
S. Nilsson and D. J. Grove, “Adrenergic and cholinergic innervation of the spleen of the cod: Gadus morhua,” European Journal of Pharmacology, vol. 28, no. 1, pp. 135–143, 1974.
[57]
R. Fange and S. Nilsson, “The fish spleen: structure and function,” Experientia, vol. 41, no. 2, pp. 152–158, 1985.
[58]
M. Dunier, A. K. Siwicki, and A. Demael, “Effects of organophosphorus insecticides: effects of trichlorfon and dichlorvos on the immune response of carp (Cyprinus carpio). III. In vitro effects on lymphocyte proliferation and phagocytosis and in vivo effects on humoral response,” Ecotoxicology and Environmental Safety, vol. 22, no. 1, pp. 79–87, 1991.
[59]
M. I. Girón-Pérez, A. Santerre, F. Gonzalez-Jaime et al., “Immunotoxicity and hepatic function evaluation in Nile tilapia (Oreochromis niloticus) exposed to diazinon,” Fish & Shellfish Immunology, vol. 23, no. 4, pp. 760–769, 2007.
[60]
M. I. Girón-Pérez, G. Zaitseva, J. Casas-Solis, and A. Santerre, “Effects of diazinon and diazoxon on the lymphoproliferation rate of splenocytes from Nile tilapia (Oreochromis niloticus): the immunosuppresive effect could involve an increase in acetylcholine levels,” Fish & Shellfish Immunology, vol. 25, no. 5, pp. 517–521, 2008.
[61]
Y. Horiuchi, R. Kimura, N. Kato et al., “Evolutional study on acetylcholine expression,” Life Sciences, vol. 72, no. 15, pp. 1745–1756, 2003.
[62]
T. Fujii and K. Kawashima, “An independent non-neuronal cholinergic system in lymphocytes,” Japanese Journal of Pharmacology, vol. 85, no. 1, pp. 11–15, 2001.
[63]
K. Kawashima and T. Fujii, “The lymphocytic cholinergic system and its contribution to the regulation of immune activity,” Life Sciences, vol. 74, no. 6, pp. 675–696, 2003.
[64]
K. Kawashima, T. Fujii, Y. Moriwaki, H. Misawa, and K. Horiguchi, “Reconciling neuronally and nonneuronally derived acetylcholine in the regulation of immune function,” Annals of the New York Aacademy of Sciences, vol. 1261, pp. 7–17, 2012.
[65]
C. Reardon, G. S. Duncan, A. Brüstle et al., “Lymphocyte-derived ACh regulates local innate but not adaptive immunity,” Annals of the New York Academy of Sciences, vol. 110, no. 4, pp. 1410–1415, 2013.
[66]
S. Neumann, M. Razen, P. Habermehl et al., “The non-neuronal cholinergic system in peripheral blood cells: effects of nicotinic and muscarinic receptor antagonists on phagocytosis, respiratory burst and migration,” Life Sciences, vol. 80, no. 24-25, pp. 2361–2364, 2007.
[67]
Y. Okuma and Y. Nomura, “Roles of muscarinic acetylcholine receptors in interleukin-2 synthesis in lymphocytes,” Japanese Journal of Pharmacology, vol. 85, no. 1, pp. 16–19, 2001.
[68]
M. Behra, X. Cousin, C. Bertrand et al., “Acetylcholinesterase is required for neuronal and muscular development in the zebrafish embryo,” Nature Neuroscience, vol. 5, no. 2, pp. 111–118, 2002.
[69]
L. E. Hightower and J. L. Renfro, “Recent applications of fish cell culture to biomedical research,” Journal of Experimental Zoology, vol. 248, no. 3, pp. 290–302, 1988.
[70]
R. N. Winn, “Transgenic fish as models in environmental toxicology,” ILAR Journal, vol. 42, no. 4, pp. 322–329, 2001.
[71]
A. R. Cossins and D. L. Crawford, “Fish as models for environmental genomics,” Nature Reviews Genetics, vol. 6, no. 4, pp. 324–333, 2005.
[72]
J. Keesey, “How electric fish became sources of acetylcholine receptor,” Journal of the History of the Neurosciences, vol. 14, no. 2, pp. 149–164, 2005.
[73]
M. Zouridakis, P. Zisimopoulou, K. Poulas, and S. J. Tzartos, “Recent advances in understanding the structure of nicotinic acetylcholine receptors,” IUBMB Life, vol. 61, no. 4, pp. 407–423, 2009.
[74]
S. Santana, E. P. Rico, and J. S. Burgos, “Can zebrafish be used as animal model to study Alzheimer's disease?” American Journal of Neurodegenerative Diseases, vol. 1, no. 1, pp. 32–48, 2012.
[75]
E. D. Levin and E. Chen, “Nicotinic involvement in memory function in zebrafish,” Neurotoxicology and Teratology, vol. 26, no. 6, pp. 731–735, 2004.
[76]
J. Osswald, A. P. Carvalho, L. Guimar？es, and L. Guilhermino, “Toxic effects of pure anatoxin-a on biomarkers of rainbow trout, Oncorhynchus mykiss,” Toxicon, vol. 70, pp. 162–169, 2013.
[77]
K. R. Pawar, “Toxic of teratogenic effect of fenitrothion, BHC and carbofuran on the embryonic development of Cyprinus carpio communis,” Environment and Ecology, vol. 12, no. 2, pp. 284–287, 1994.
[78]
R. N. Ram and S. K. Singh, “Carbofuran-induced histopathological and biochemical changes in liver of the teleost fish, Channa punctatus (Bloch),” Ecotoxicology and Environmental Safety, vol. 16, no. 3, pp. 194–201, 1988.
[79]
J. T. Zelikoff, “Biomarkers of immunotoxicity in fish and other non-mammalian sentinel species: predictive value for mammals?” Toxicology, vol. 129, no. 1, pp. 63–71, 1998.
[80]
M. I. Girón-Pérez, J. Velázquez-Fernández, K. Díaz-Resendiz et al., “Immunologic parameters evaluations in Nile tilapia (Oreochromis niloticus) exposed to sublethal concentrations of diazinon,” Fish & Shellfish Immunology, vol. 27, no. 2, pp. 383–385, 2009.
[81]
M. I. Girón-Pérez, R. Barcelós-García, Z. G. Vidal-Chavez, C. A. Romero-Ba？uelos, and M. L. Robledo-Marenco, “Effect of chlorpyrifos on the hematology and phagocytic activity of Nile tilapia cells (Oreochromis niloticus),” Toxicology Mechanisms and Methods, vol. 16, no. 9, pp. 495–499, 2006.
