Immunostimulatory and immunoadjuvant capacities of soluble Rhamnan-type Ulva oligosaccharides

Algae polysaccharides were discovered to act as pathogen-associated molecular patterns (PAMPs) to trigger immune responses, while bioactivities of oligosaccharides have not been thoroughly explored. Ulva oligosaccharides from Ulva prolifera were obtained using PL25 family ulvan lyase and evaluated for cell viability and phagocytic activity. Ulva oligosaccharides with 542 Da (OUP), consisting of tetrasaccharide (∆UA-RhaS-Xyl-RhaS) and disaccharides (∆UA-RhaS), exhibited the most pronounced phagocytic activities. Besides, OUP could effectively stimulate the expressions of proinflammatory cytokines and chemokines like TNF-α, IL-1β, IL-6, IFN-γ and CXCL1 in primary macrophages and subsequently promote the proliferation and activation of T and B lymphocytes in vitro. Transcriptome analysis also gave rise to the systemic proinflammatory responses triggered by OUP in macrophages, such as activation of multiple PRRs-related signaling pathways and downstream JAK-STAT and NF-κB signaling. Furthermore, in an in vivo mouse OVA immunization model, OUP upregulated the specific anti-OVA IgG antibody production in vivo, pointing to its immunoadjuvant capacity. OUP increases cell proliferation and secretion of IL-4 and IFN-γ of splenocytes in response to OVA stimulation ex vivo, thereby enhancing both Th1 and Th2 immune responses. Collectively, all this data suggests that OUP could function as the immune stimulator to enhance host immune response to infections.