Long-lived effects of administering β-glucans: Indications for trained immunity in fish.

Over the past decades, it has become evident that immune-modulation of fish with β-glucans, using injection, dietary or even immersion routes of administration, has stimulating but presumed short-lived effects on both intestinal and systemic immunity and can increase protection against a subsequent pathogenic challenge. Although the exact effects can be variable depending on, among others, fish species and administration route, the immune-stimulating effects of β-glucans on the immune system of fish appear to be universal. This review provides a condensed update of the most recent literature describing the effects of β-glucans on the teleost fish immune system. We shortly discuss possible mechanisms influencing immune-stimulation by β-glucans, including microbial composition of the gut, receptor recognition and downstream signalling. Of interest, in mammalian monocytes, β-glucans are potent inducers of trained immunity. First, we screened the literature for indications of this phenomenon in fish. Criteria that we applied include indications for at least one out of three features considered characteristic of trained immunity; (i) providing protection against a secondary infection in a T- and B-lymphocyte independent manner, (ii) conferring increased resistance upon re-infection and, (iii) relying on key roles for innate immune cell types such as natural killer cells and macrophages. We conclude that several indications exist that support the notion that the innate immune system of teleost fish can be trained. Second, we screened the literature for indications of long-lived effects on innate immunity of fish after administering β-glucans, a criterion which could help to identify key roles for macrophages on resistance to infection. We discuss whether β-glucans, as well-known immune-stimulants, are able to train the immune system of fish and argue in favour of further studies designed to specifically investigate this phenomenon in fish.