Differential Binding of ΔFN3 Proteins of <em>Bifidobacterium longum</em> GT15 and <em>Bifidobacterium bifidum</em> 791 to Cytokines Determined by Surface Plasmon Resonance and <em>de Novo</em> Molecular Modeling

Bifidobacteria, a genus of obligate anaerobes, comprise a major component of the intestinal microbiota. Importantly, bifidobacteria participate in the immune reactions. These bacteria carry a species-specific operon in which the fn3 gene encodes a multifunctional protein FN3 that mediates the bacterial adhesion to the intestinal epithelium and is capable of binding individual cytokines. Bioinformatics and biochemical approaches were used to study the possible interaction of recombinant protein fragments ∆FN3 of B. longum and B. bifidum strains with cytokines TNF-α, IL-6, IL-8 and IL-10. De novo molecular modeling generated, for the first time, the structural models of species-derived ∆FN3 proteins and revealed new tentative regions for differential cytokine binding. Combined treatment with ∆FN3 and TNF-α induced TNF-α mRNA abundance in the human monocytic cell line. Altogether, these findings provide structural evidence for regulation of immune reactions by microbiota-derived proteins.