Diverse immunological benefits mediated by fungal mannan through enhancement of plasma cell differentiation and protective antibody responses: implications in the fungi-host mutualism 4184

Abstract Description Fungal cell wall acts as a major interface with the host immune system. Whether its components have a direct impact on B cell differentiation is poorly understood, in contrast to the well-documented induction of class switch DNA recombination (CSR) and plasma cell differentiation by TLR ligands derived from bacterial cell wall or viral genome replication intermediates. Here we showed that fungal polysaccharide mannan, but not β-1,3-glucan or polysaccharide/protein complex zymosan, played an important role in the control of systemic infection by E. coli, intestinal tract infection by Salmonella and colitis induced by dextran sulfate sodium (DSS) in mice. Such protective effects by intra-rectally administered mannan were dependent on the presence of B cells and IgA production, consistent with mannan enhancement of antibody-secreting plasma cells and IgA responses. Mechanistically, while none of the fungal cell wall component could activate murine B cells or significantly affected TLR- or CD40-induce CSR, mannan (but not β-1,3-glucan or zymosan) potentiated TLR4 induced generation of plasma cells, including those that secreted class-switched IgA and IgG. It did so by enhancing NF-κB activation, increasing the expression of XBP1 and pro-survival genes, and boosting plasma cell survival. Overall, the diverse immunological benefits endowed by mannan through plasma cell survival and IgA antibody responses likely underpin the mutualism between commensal fungi and the host. Funding Sources Supported by NIH/NIAID R21 AI135599-02; NIH/NIAID R01 AI153506-A1; Crohn’s & ColitisFoundation Senior Research Award Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)