Host Cell Vimentin Restrains Toxoplasma gondii Invasion and Phosphorylation of Vimentin is Partially Regulated by Interaction with TgROP18

He, Cheng; Kong, Ling; Zhou, Lijuan; Xia, Jing; Wei, Haixia; Liu, Min; Peng, Hongjuan

Host cell vimentin has been demonstrated to function in facilitating the infection of some adhesive or invasive microbial pathogens, including P. multocida and African swine fever virus [29, 30] . Moreover, vimentin is identified as a novel NF-κB regulator and is involved in modulating the NF-κB signaling pathway to influence invasion of pathogens, such as E. coli K1 [31, 32] . The disassembly of vimentin caused by treatment with high concentrations of the phosphatase inhibitors, okadaic acid and calyculin A, suggests that vimentin's assembly/disassembly is regulated by its phosphorylation and dephosphorylation [20] . The assembly and solubility of vimentin are regulated by the phosphorylation/dephosphorylation of vimentin at Ser38 and Ser55 induced by Rab7a [33] . Moreover, phosphorylation level of vimentin Ser38 was significantly upregulated in host cell infected with T. gondii at both 2h and 6h comparing to host cell without T. gondii infection [34] . Consistent with the above reports, higher vimentin expression corresponding to much lower solubility in host cell with T. gondii infection for 2h and 6h, which also suggest that vimentin phosphorylation is associated with its solubility. The reorganization of cellular vimentin is also affected by its solubility, which is, in turn, regulated by its phosphorylation [35, 36] . Progressive rearrangement of vimentin around the enlarging PVs was reported at 30min, 12h, and 18h post-infection [20] , and vimentin forms a dynamic, flexible network and contributes to maintenance of the integrity of the cellular actin cytoskeleton [37] . Consistent with previous findings, a significant rearrangement of vimentin was also observed in our study in cells infected with T. gondii for different periods of time (1, 2, 6, 12, and 22h) post-infection, from invasion to multiplication (Figure 2) , and variable changes in vimentin solubility, phosphorylation, and expression levels were also observed during T. gondii infection at different time points (1, 2, 6, 12,24, 36, and 48h) (Figure 3 ).