Dectin-1 Facilitates IL-18 Production for the Generation of Protective Antibodies AgainstCandida albicans

Invasive candidiasis (IC) is one of the leading causes of death among immunocompromised patients. Because of limited effective therapy treatment options, prevention of IC through vaccine is an appealing strategy. However, how to induce the generation of direct candidacidal antibodies in host remains unclear.Gpi7mutantC. albicansis an avirulent strain that exposes cell wall beta-(1,3)-glucans. Here, we found that vaccination with thegpi7mutant strain could protect mice against invasive candidiasis caused byC. albicansand non-albicans Candidaspp. The protective effects induced bygpi7mutant relied on long-lived plasma cells (LLPCs) secreting protective antibodies againstC. albicans. Clinically, we verified a similar profile of IgG antibodies in the serum samples from patients recovering from IC to those fromgpi7mutant-vaccinated mice. Mechanistically, we found cell wall beta-(1,3)-glucan ofgpi7mutant facilitated Dectin-1 receptor dependent nuclear translocation of non-canonical NF-kappa B subunit RelB in macrophages and subsequent IL-18 secretion, which primed protective antibodies generationin vivo. Together, our study demonstrate that Dectin-1 engagement could trigger RelB activation to prime IL-18 expression and established a new paradigm for consideration of the link between Dectin-1 mediated innate immune response and adaptive humoral immunity, suggesting a previously unknown active vaccination strategy againstCandidaspp. infection.