Micro- and macroalgae blend modulates the mucosal and systemic immune responses of European seabass (Dicentrarchus labrax) upon infection with Tenacibaculum maritimum

Intensification of aquaculture practices is often associated with disease outbreaks. These outbreaks can heavily affect the production of several fish species such as European seabass (Dicentrarchus labrax) that is of high economic relevance in Mediterranean countries. Nutritional approaches are promising solutions to alleviate the burden caused by diseases. In this context, algae-derived bioactive compounds, which can stimulate fish's immune system, should be considered to elevate the health status of farmed fish. Here we thoroughly evaluated the immunomodulatory activity of a commercially produced micro- (Nannochloropsis oceanica and Chlorella vulgaris) and macroalgae (Gracilaria gracilis and Ulva rigida) blend, both at the systemic and mucosal levels, focusing on the protective potential against Tenacibaculum maritimum, a pathogen heavily affecting farmed seabass. A commercial-based diet rich in plant proteins (CTRL) was compared against 3 experimental diets (blend 2, 4 and 6) with increasing levels of the algae blend (2, 4 and 6% inclusion, respectively). After a 12-weeks feeding trial, European seabass juveniles were subjected to a bath challenge with T. maritimum and relocated to two new systems: one system to collect tissues 48 h post-infection, and a second system to register mortalities over 8 days. The results indicate that the algae blend is able to improve fish growth performance and evoke appropriate mucosal immune response upon infection with T. maritimum. The blend promoted a more exacerbated immune response, in a dose-dependent manner, by favoring the migration of monocytes and lymphocytes to mucosal tissues, which are the first sites to be affected by the pathogen. Such cellular responses were accompanied by an upregulation of genes associated with cell migration and proliferation (mmp9 and pcna), and pro-inflammatory responses (il-1β and il-8) in skin and gut tissues. At the systemic level, all blend diets elevated the plasma bactericidal activity and increased the expression of the antimicrobial peptide hepcidin in the head-kidney. The 4% incorporation level, but not the other levels, also led to a higher number of circulating peripheral neutrophils and acidic goblet cells in the intestine. Altogether, and although all blend diets improved fish growth and had some immunomodulatory effects, the 4% inclusion level seems the most suitable to prevent the adhesion and colonization of the pathogen on mucosal tissues, thereby inhibiting the progression of the disease and reducing mortality upon a challenge with T. maritimum. The present results highlight the importance of the mucosal immune response during bacterial infection and the potential of algae to modulate the mucosal immunity.