Main Components of Fish Immunity - 5. Mucosal Barriers

5. Mucosal Barriers

Fish can interact with their surroundings through mucosal barriers while still maintaining homeostasis. Mucosal barriers (Figure 1) are extremely complex tissues with special adaptations that enhance a variety of physiological functions, including immunity, gas exchange, and nutrition.

 

interact 상호작용하다

homeostasis 항상성

 physiological 생리학적으로

 

Figure 1. Schematic representation of the fish mucosal immunity.

 

 

The principal mucosa-associated lymphoid tissues (MALTs) of teleosts are the gut-associated lymphoid tissue (GALT), gill-associated lymphoid tissue (GIALT), skin-associated lymphoid tissue (SALT), and nasopharynx-associated lymphoid tissue (NALT).

 

mucosa 점막

gut 소화관

nasopharynx 비인두

nasopharynx 비인두: the upper part of the pharynx, connecting with the nasal cavity above the soft palate.

 

These component mucosal barriers serve as the host’s local immune system and protect it from pathogens and other threats. The fish MALT possesses the major populations of innate immune cells, as well as the lymphocyte populations of CD4 and CD8 T cells, and B cells [3].

 

 

However, only three immunoglobulins’ (Igs) isotypes have been discovered in teleost to date (IgM, IgD, and IgT/Z), each of which consists of two identical heavy and two identical light polypeptide chains [123].

 

IgT/Z is thought to be specialized in the mucosal immunity. In mammalian mucosal surfaces, the main immunoglobulin is IgA, which is mostly produced by plasma cells present in the gut lamina propria. In a similar way, the teleost IgA homologue, IgT/IgZ, has a dominant role in gut mucosal immunity [124].

 

The transport of IgM and IgT through mucosal barriers is carried out by the polymeric immunoglobulin receptor (pIgR), which is also expressed in the gut and skin of teleosts [125]. In zebrafish and rainbow trout, dendritic-like cells have recently been identified [94]. It is intriguing that DCs only make up around 15% of the mononuclear phagocytes in the skin of adult zebrafish but are sparse in the gut, spleen, and kidney [126].

 

It has been hypothesized that zebrafish skin has DCs comparable to mammalian Langerhans cells [127]. Additionally, innate immune genes such as TNF have been found in the mucosal tissues, indicating that innate immunity has a role in the antiviral process [128].

 

5.1. Fish Mucus

Fish mucus that covers the mucosal surface is produced by many types of secretory cells, mainly the goblet cells (GCs), sacciform cells, and club cells. Goblet cells, which produce mucus granules and contain glycoproteins, are prevalent on all external surfaces, as well as the surface of the gills [129].

 

secretory cell 분비세포

mucus granule 점액과립

 

The initial line of defense against pathogen invasion is fish mucus [130]. Mucins are the major molecules found in mucus and are responsible for the mucus viscosity, pathogen entrapment, physical protection of the skin’s surface, and signaling at the cell surface. Mucins are a heterogeneous family of high molecular weight glycoproteins with single or many protein domains that have numerous locations where O-glycan attachment can be formed.

 

 viscosity 점도

 pathogen entrapment 병원체 포획

 

Mucins contribute to the innate immune system in two ways that are significant. First, they prevent the adhesion of pathogens, sustained colonization of potentially infectious bacteria, and invasion of parasites by being continuously generated and routinely shed [131].

 

adhesion 접착력

potentially 가능성

 

Second, they contain a variety of innate immunity-related proteins and enzymes, including lysozyme, esterases, complement proteins, lectins, C-reactive protein (CRP), transferring, alkaline phosphatise (ALP), proteases, immunoglobulins, and antimicrobial peptides (AMPs), and various other antibacterial proteins and peptides, which are frequently responsible for deteriorating, inactivating, and controlling infections [132,133].

 

In addition, the fish skin mucus has been reported to have few metabolites with antibacterial properties such as N-acetylneuraminic acid, azelaic acid, and hydroxyisocaproic acid [134].

 

 metabolite 대사산물

 

According to reports, fish skin mucus contains a variety of saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs). Palmitic acid and stearic acid are SFAs that are present in mucus. Oleic acid is an example of a monosaturated fatty acid. Moroctic and alpha-linolenic acids are polyunsaturated fatty acids. These fatty acids are thought to perform a significant defensive function against pathogens [135].

 

Skin transcriptome analysis of S. trutta, M. anguillicaudatus, and C. striatus demonstrated that several genes are implicated in immunology and epidermal mucus secretion. Mucins are divided into two structurally separate families: membrane bound and large secreted gel forming (SGFM) forms, and, to date, more than 20 mucin genes have been identified in higher vertebrates [136].

 

Cystein-rich (C8) and trypsin inhibitor-like cysteine-rich (TIL) domains are two of the domain structures that distinguish the secreted gel-forming mucins from other types. These domains aid in the disulfide bond formation that leads to the oligomerization of the mucin proteins, which gives mucus its ability to gel. Additionally, long repetitive sequences rich in proline, threonine, and serine residues, known as the PTS-domain, are present in the released gel-forming mucins [137,138].

 

MUC2, MUC5AC, MUC5B, MUC6, and MUC19 are examples of SGFM. However, the membrane-bound mucins include MUC1, MUC3, MUC4, MUC12, MUC13, MUC14, MUC15, MUC16, MUC17, and MUC18 [139]. The mucin genes of a few teleost fish species, such as zebrafish (Danio rerio) [140], gilthead sea bream (Sparus aurata) [141], common carp (Cyprinus carpio) [142], and sea trout (Salmo trutta), have been discovered [143].

 

Seven secreted gel-forming mucin genes were discovered in the Atlantic salmon based on many levels of evidence, including annotation, transcription, phylogeny, and domain structure. Five genes were labelled as muc5 and two as muc2. The muc5 genes were largely expressed on the epidermis and gills, while the muc2 genes were primarily expressed in the intestinal region [144].

 

The mucus cells and the composition of the mucus are influenced by several exogenous (e.g., hyperosmolarity, stress, infections, and pH) and endogenous (e.g., developmental stage, sex) factors [31].

 

The properties of the mucus vary among fish species, and they are subject to change in response to disease and environmental factors. Amoebic gill disease (AGD) is one of the main disorders affecting the mariculture of Atlantic salmon (Salmo salar L.). AGD is characterized by increased gill mucus production and hyperplasia of the lamellar epithelium. The regulation of two mucins (muc5, muc18) changed in response to illness. The secreted muc5 was significantly upregulated in AGD, but the membrane-bound muc18 showed the reverse pattern [145].

 

Surprisingly, the properties of the skin mucus of carp appear to alter in response to increases in the total amount of bacteria in the water. Increases in acidic glycoconjugates and overall glycosylation can be noticed as changes in the terminal presence of certain sugars [146]. Similar to this, myxozoan parasite infection alters the characteristics of seabream (Sparus aurata) gut mucus, resulting in higher levels of glycosylation and terminal glycosylation of mucus proteins in the posterior gut [147].

 

The fish mucus has a wide range of functions, including protection, respiration, disease resistance, as well as osmotic regulation, excretion, reproduction, communication, nest building, and feeding. Fish mucus extract is increasingly known to possess a wide range of biological qualities, for instance, antiviral, antibacterial, antiparasitic, and antifungal qualities, which may be employed in both human medicine and fish farming [148].

 

Sacciform cells and acidophilic granular cells (orserous goblet cells) have also been demonstrated in fish skin whose secretions mix with the secretions of goblet cells to form mucus. Sacciform cells may be analogous to granular glands of amphibians, which produce crinotoxic and repellent substances, but secretions of these cells also have a protective and regulatory role [149].

 

On the other hand, the adaptive immune components include Igs, which are expressed on the B cells’ surface as B cell receptors or in a soluble form in body fluids [150]. Moreover, these mucosal Igs (secretory Igs “sIgs”) are widespread in the mucosal barriers of teleosts, including the gut [124], olfactory organ [151], gills [152], skin [153], and buccal and pharyngeal cavities [154].

 

Recently, a bursa of Fabricius-like structure in Atlantic salmon (Salmo salar) cloaca was identified where IgT+ and IgM+ B cells could be distinguished, which indicates that sIgs may be secreted into the mucus around this structure [155].

 

The expressions of constituents involved in the cholinergic system, including acetylcholinesterase (ChAT) and vesicular ACh transporter (VAChT), have been confirmed in various immune cells including macrophages and epithelial cells [156]. Several studies have demonstrated that most epithelial cells do not concentrate ACh into vesicles; instead, they release it directly from the cytoplasm [157].

 

5.2. The Intestinal Mucosa

The intestinal mucosa of teleosts is a saturated substrate for leukocytes, and they are housed within the lamina propria [78]. These strata contain proliferating granulocytes, lysozyme, and NK cells, which together promote the production of lysozyme and superoxides [158,159]. The epithelial cells also play the role of a secondary barrier, securing the passage while permitting proper nutrient flows, signaling permeability, and benefiting gut microflora to improve digestion [160]. The intestinal regions possess an essential population of immunoglobulins and isolated populations of both T and B cells, called intra-epithelial lymphocytes (IELs) [161]. Dezfuli et al. [162] have found that mast-cell analogues have a role in the indirect propagation of immunoglobulins following viral infection. Inami et al. [163] found a larger number of IgM-positive cells in the rectum of Atlantic cod (Gadus morhua), compared with the stomach regions and foregut. This result agrees with the familiar adaptive immunocompetency of the posterior intestine and demonstrates the capability of Igs to aggregate in specific regions away from common GALT. As fish lack IgA, serum or secretory immunoglobulin, IgM is rapidly degraded within the harsh environment [164].