To React or Not to React: The Dilemma of Fish Immune Systems Facing Myxozoan Infections

Abstract

Myxozoans are microscopic, metazoan, obligate parasites, belonging to the phylum Cnidaria. In contrast to the free-living lifestyle of most members of this taxon, myxozoans have complex life cycles alternating between vertebrate and invertebrate hosts. Vertebrate hosts are primarily fish, although they are also reported from amphibians, reptiles, trematodes, mollusks, birds and mammals. Invertebrate hosts include annelids and bryozoans. Most myxozoans are not overtly pathogenic to fish hosts, but some are responsible for severe economic losses in fisheries and aquaculture. In both scenarios, the interaction between the parasite and the host immune system is key to explain such different outcomes of this relationship. Innate immune responses contribute to the resistance of certain fish strains and species, and the absence or low levels of some innate and regulatory factors explain the high pathogenicity of some infections. In many cases, immune evasion explains the absence of a host response and allows the parasite to proliferate covertly during the first stages of the infection. In some infections, the lack of an appropriate regulatory response results in an excessive inflammatory response, causing immunopathological consequences that are worse than inflicted by the parasite itself. This review will update the available information about the immune responses against Myxozoa, with special focus on T and B lymphocyte and immunoglobulin responses, how these immune effectors are modulated by different biotic and abiotic factors, and on the mechanisms of immune evasion targeting specific immune effectors. The current and future design of control strategies for myxozoan diseases is based on understanding this myxozoan-fish interaction, and immune-based strategies such as improvement of innate and specific factors through diets and additives, host genetic selection, passive immunization and vaccination, are starting to be considered.

Keywords: B lymphocytes; RNAseq; T lymphocytes; adaptive immunity; immune evasion; immunoglobulin; parasite; teleost.

Figure 1

Graph showing the increasing trend of myxozoan publications found in the Web of Science (WOS) from 1900 to 2020. The search terms were: Myxozoa or Myxosporea or Actinosporea or Malacosporea (blue circles). The first article found in this database was in 1978. Among them, immunology related articles however appeared later in 1993, with a minor number, but also with an increasing trend (orange circles).

Figure 2

Micro and macro photographs of the main seven myxozoan species for which information is available on fish adaptive immune response. Pictures in the left column (A, D, G, J, M, P, S) fresh smears of myxospores, except for T. bryosalmonae in which a proliferative stage is shown (S). Middle column refers to clinical signs: note the sunken head syndrome in turbot (arrow in B), the sunken belly and prominent head bones in gilthead sea bream (arrowheads in E), the myoliquefaction in a mackerel (H), the black tail in rainbow trout (K), the swollen and ascitic digestive tract in rainbow trout (N), the pale gills and splenomegaly in common carp (arrows in Q), the swollen kidney and splenomegaly in rainbow trout (arrows in T). The right column depicts histopathological aspects. Catarrhal enteritis in turbot (C, Giemsa); invasion of the paracellular space of the gut (Giemsa, F); hypertrophy of myocytes (I, toluidine blue); invasion of the cartilage of rainbow trout (L, Giemsa); destruction of the intestine with detachment of stages to the lumen (Q, H, E); sporogony in the gill epithelium [R, in situ hybridisation with parasites labelled in by VectorBlue, counterstained with Neutral red, according to Eszterbauer et al. (25)]; interstitial stages in a kidney imprint (V, Diff-Quick). Scale bars: 10 µm (A, C, D, F, G, J, M, P, S); 20 µM (I, O, V); 50 µM (L, R). Illustrations courtesy of C. Zarza, ARC Skretting (B); M. Kent, Oregon State University, USA (G); S. Hallet, Oregon State University, USA (K); S. Atkinson, Oregon State University, USA (M); E. Eszterbauer, Hungarian Academy of Sciences (P). The remaining figures are from the authors.

Figure 3

Microphotographs depicting the specific immune response against some myxozoans. (A) Turbot intestine infected by E. scophthalmi showing abundant IgM+ cells in the lamina propria submucosa, immunostained with a monoclonal antibody. (B–D) Panoramic and close ups of gilthead sea bream intestines infected with E. leei showing abundant IgM (blue) and IgT (magenta) positive cells. RNA-in situ hybridization (RNA-ISH) was used to detect transcripts of IgM and IgT as indicated in Picard-Sánchez et al. (134). (E) Rainbow trout kidney infected with T. bryosalmonae showing abundant IgM+ cells and (F) IgT+ positive cells. Sections were immunostained as indicated in Abos et al. (135). (G) Large accumulations of IgT+ B cells in the gut lamina propria and epithelium of rainbow trout surviving infection by C. shasta. Immunofluorescence staining of a gut cryosection from rainbow trout, three months post-infection with C. shasta. Cryosection was stained for IgM (red), IgT(green) and C. shasta (magenta); nuclei were stained with DAPI (blue). Parasites can be seen within the gut lumen. (H) S. molnari multicellular blood stage surrounded by B cells labelled for IgM (yellow) and stained with DAPI (blue). Scale bars: 10 µm (D-H); 20 µm (A, C); 100 µm (B). Illustrations courtesy of R. Bermúdez, USC, Spain (A); C. Tafalla, INIA, Spain (E, F); O. Sunyer, University of Pennsylvania, USA (G). The remaining figures are from the authors.

Figure 4

Photomicrographs showing immune evasion strategies. (A) Small sporogonic plasmodia of Myxobolus sp. inside a nerve strand in the muscle of brown trout (Giemsa-stained). (B) Plasmodium of Chloromyxum sp. floating in the bile without contact to host tissues (fresh preparation). (C) Typical interstitial stage of T. bryosalmonae in the kidney of rainbow trout, located within a single phagocyte (kidney imprint, Diff-Quick-stained; nucleus of phagocyte indicated by arrow). (D) Folds on the surface of a primary cell of S. molnari blood stage, which promote twitching motility (SEM). (E) Intravascular plasmodium of Myxobolus sp. whose outer margin is lined with host cells which are inserted into the microvillar surface of the plasmodium. Scale bars: 10 µm (A–C); 5 µm (D); 20 µm (E). Illustration (B) courtesy of A Lövy, Biology Centre of the Czech Academy of Sciences. The remaining figures are from the authors.