Mucosal immunoglobulins of teleost fish: A decade of advances

Abstract

Immunoglobulins (Igs) are complex glycoproteins that play critical functions in innate and adaptive immunity of all jawed vertebrates. Given the unique characteristics of mucosal barriers, secretory Igs (sIgs) have specialized to maintain homeostasis and keep pathogens at bay at mucosal tissues from fish to mammals. In teleost fish, the three main IgH isotypes, IgM, IgD and IgT/Z can be found in different proportions at the mucosal secretions of the skin, gills, gut, nasal, buccal, and pharyngeal mucosae. Similar to the role of mammalian IgA, IgT plays a predominant role in fish mucosal immunity. Recent studies in IgT have illuminated the primordial role of sIgs in both microbiota homeostasis and pathogen control at mucosal sites. Ten years ago, IgT was discovered to be an immunoglobulin class specialized in mucosal immunity. Aiming at this 10-year anniversary, the goal of this review is to summarize the current status of the field of fish Igs since that discovery, while identifying knowledge gaps and future avenues that will move the field forward in both basic and applied science areas.

Keywords: Immunoglobulins; Microbiota; Mucosal immunity; Mucosal vaccines; Teleosts.

Figure 1:. Schematic representation of the different direct and indirect mechanisms by which sIg coating contributes to microbiota homeostasis at fish mucosal barriers.

Figure 2:. Testing for the existence of a common mucosal immune system (CMIS) in teleosts.

Hypothetical models for B cell activation and antigen-specific sIg production in teleost fish in response to infection. In Model 1, infection of one MALT (the gut), results in local activation and proliferation of B cells as well as production of sIgs. Activated B cells would then migrate to other MALTs. Here the gut would be the inductor site, and only skin and gills are depicted as effector sites but all other MALTs would behave in a similar fashion. In Model 2, infection at one MALT, in this case the gut, only results in local activation and proliferation of B cells but no migration of activated B cells to other MALT. Thus, sIg production is restricted to the site of infection. In Model 3, infection may result in antigen transport to the spleen where B cell activation and proliferation would take place first. Next, B cells would migrate to all MALTs where they would differentiate into plasma cell and produce sIgs. All these models are only hypothetical and further experimental evidence is currently needed to support or refute them.