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Volume 11
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10.3390/fishes11060359
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Article

Neuroimmune Interactions in the Intestine of Goldfish (Carassius auratus): Insights into Enteric Neurons and Immune Cell Organization

by
Doaa M. Mokhtar
1,2,*,
Eugenia Rita Lauriano
3,
Marialuisa Aragona
4,
Hailah M. Almohaimeed
5,
Nashmiah S. Alshammari
6,
Anthea Miller
7,
Tahani A. Al-Matrafi
8,
Maria Cristina Guerrera
4,
Giorgia Pia Lombardo
3,
Adriana Nunnari
3 and
Giacomo Zaccone
9,*
1
Department of Cell and Tissues, Faculty of Veterinary Medicine, Assiut University, Assiut 71526, Egypt
2
Department of Histology and Anatomy, School of Veterinary Medicine, Badr University in Assiut, Assiut 71511, Egypt
3
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy
4
Zebrafish Neuromorphology Lab, Department of Veterinary Sciences, University of Messina, 98168 Messina, Italy
5
Department of Basic Science, College of Medicine, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia
6
Department of Biology, College of Sciences, University of Ha’il, Ha’il 81411, Saudi Arabia
7
Department for the Promotion of Human Sciences and Quality of Life, San Raffaele University, 00166 Rome, Italy
8
Anatomy Department, College of Medicine, King Saudi University, Riyadh 11461, Saudi Arabia
9
Department of Veterinary Sciences, University of Messina, 98168 Messina, Italy
*
Authors to whom correspondence should be addressed.
Fishes 2026, 11(6), 359; https://doi.org/10.3390/fishes11060359
Submission received: 11 May 2026 / Revised: 7 June 2026 / Accepted: 11 June 2026 / Published: 16 June 2026
(This article belongs to the Special Issue Molecular Mechanisms of the Non-Specific Immunity of Fish When Responding to Pathogen Infections)
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Abstract

Neuroimmune interactions in the intestine are essential for maintaining tissue homeostasis, yet they remain poorly understood in teleost fish. This study investigated the structural and cellular organization of enteric neurons and immune cells in the intestine of goldfish (Carassius auratus) using semithin histology, transmission electron microscopy (TEM), and confocal immunofluorescence. Histological observations revealed a well-organized epithelium composed of enterocytes and goblet cells, with numerous lymphocytes located in the basal epithelium. Prominent gut-associated lymphoid tissue (GALT) was identified in both scattered and aggregated forms within the lamina propria and submucosa. Macrophages were widely distributed throughout all intestinal layers and were consistently found in close proximity to enteric neurons and nerve fibers. Ultrastructural analysis confirmed direct contacts between macrophages and neuronal elements. These macrophages exhibited typical phagocytic features, including lysosomes, vacuoles, and engulfed material, particularly in association with myenteric nerve fibers. Immunofluorescence analysis revealed strong expression of toll-like receptor 2 (TLR2) and major histocompatibility complex class II (MHC II) in macrophages and enterocytes, suggesting an active role in antigen recognition. Langerin-positive dendritic-like cells were identified in the submucosa, while CD4-positive lymphocytes showed partial colocalization with serotonin (5-HT). S100-positive cells also exhibited partial overlap with 5-HT, and goblet cells demonstrated serotonin immunoreactivity. In addition, inducible nitric oxide synthase (iNOS) colocalized with TLR2 in submucosal immune cells. These findings demonstrate a close structural and functional association between enteric neurons and immune cells, highlighting an integrated neuroimmune network in the goldfish intestine.
Keywords: enteric nervous system; macrophages; GALT; TLR2; MHC II; serotonin (5-HT) enteric nervous system; macrophages; GALT; TLR2; MHC II; serotonin (5-HT)
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MDPI and ACS Style

Mokhtar, D.M.; Lauriano, E.R.; Aragona, M.; Almohaimeed, H.M.; Alshammari, N.S.; Miller, A.; Al-Matrafi, T.A.; Guerrera, M.C.; Lombardo, G.P.; Nunnari, A.; et al. Neuroimmune Interactions in the Intestine of Goldfish (Carassius auratus): Insights into Enteric Neurons and Immune Cell Organization. Fishes 2026, 11, 359. https://doi.org/10.3390/fishes11060359

AMA Style

Mokhtar DM, Lauriano ER, Aragona M, Almohaimeed HM, Alshammari NS, Miller A, Al-Matrafi TA, Guerrera MC, Lombardo GP, Nunnari A, et al. Neuroimmune Interactions in the Intestine of Goldfish (Carassius auratus): Insights into Enteric Neurons and Immune Cell Organization. Fishes. 2026; 11(6):359. https://doi.org/10.3390/fishes11060359

Chicago/Turabian Style

Mokhtar, Doaa M., Eugenia Rita Lauriano, Marialuisa Aragona, Hailah M. Almohaimeed, Nashmiah S. Alshammari, Anthea Miller, Tahani A. Al-Matrafi, Maria Cristina Guerrera, Giorgia Pia Lombardo, Adriana Nunnari, and et al. 2026. "Neuroimmune Interactions in the Intestine of Goldfish (Carassius auratus): Insights into Enteric Neurons and Immune Cell Organization" Fishes 11, no. 6: 359. https://doi.org/10.3390/fishes11060359

APA Style

Mokhtar, D. M., Lauriano, E. R., Aragona, M., Almohaimeed, H. M., Alshammari, N. S., Miller, A., Al-Matrafi, T. A., Guerrera, M. C., Lombardo, G. P., Nunnari, A., & Zaccone, G. (2026). Neuroimmune Interactions in the Intestine of Goldfish (Carassius auratus): Insights into Enteric Neurons and Immune Cell Organization. Fishes, 11(6), 359. https://doi.org/10.3390/fishes11060359

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