fig2

Figure 2. Hypothetical schematic illustration of the interaction between proteins encoded by the PFNA operon of B. longum subsp. longum GT15 and elements of the host’s immune system. The Pkb2 signaling system is activated by an unknown ligand, which is most likely a component of the host’s immune system (possibly TNFα). Serine-threonine protein kinase Pkb2, following its activation by a ligand, autophosphorylated^[22,23] and phosphorylated other substrates, including the MoxR-ATPase protein encoded by the aaa-atp gene of the PFNA operon^[22]. MoxR-ATPase is a chaperone that is possibly involved in the folding of proteins, including the FN3 protein. FN3 is a secreted protein possessing a transmembrane domain that is presumably attached to the outer surface of the bacterial cell membrane. It has been experimentally shown that the ΔFN3.1 protein is capable of selective binding of the cytokine TNFα^[24]. The strain B. longum subsp. longum GT15 also increases the expression of TNFα, IL8, and IL10 cytokines in human cells^[27]. Apparently, TNFα interacts with an unknown signaling system in B. longum subsp. longum GT15 (possibly, Pkb2), upregulating the expression of the PFNA operon genes, including the fn3 gene encoding the FN3 protein^[25], which is capable of binding TNFα^[24]. Figure 2 offers a putative mechanism of bidirectional interaction between Bifidobacterium and the human immune system.