Pathogenic Bacteria Mediated Host Innate Immune Response Requires A Rif-dependent Pathway

The Rho subfamily of small G proteins plays critical roles in cell morphology,movement,and adhesion by dynamic regulation of actin cytoskeleton.At the sametime,the small Rho GTPases can also affect cell proliferation and immune responses by regulating gene expression.It is known that the small Rho GTPase Rif(Rho in filopodia)can regulate the formation of filopodia structure,but it is still unclear whether it can participate in the intracellular immune regulation processes.After demonstrating that Rif can promote the activation of NF-?B,we further revealed that ligands such as LPS,HKSA and virulence factor SopE cound function as Rif activators.Furthermore,it was found that Rif interacted with cell membrane PRR TLR4 or TLR2 in a time-dependent manner exposed to LPS or HKSA.Subsequently,PKC was recruited to stimulate NF-?B activation.Moreover,cytoplasmic PRR NOD1 can detect the activation state of Rif.Overexpression of continuously activated form of Rif activated NOD1 or NOD1-containing nodosome complexes,followed by RIP2(also known as RIPK2)-mediated NF-?B-dependent inflammatory responses.It is the very first time to reveal that Rif is indispensable for pattern-recognition receptor-mediated anti-bacterial innate immune responses.