Human pathogenic fungus Trichophyton schoenleinii activates the NLRP3 inflammasome

The fungus Trichophyton schoenleinii(T.schoenleinii)is the causative agent of Trichophytosis and Tinea favosa of the scalp in certain regions of Eurasia and Africa.Hu-man innate immune system plays an important role in combating with various pathogens including fungi.The inflammasome is one of the most critical arms of host innate immunity,which is a protein complex controlling maturation of IL-1β.To clarify whether T.schoenleinii is able to activate the infl ammasome,we analyzed human monocytic cell line THP-1 for IL-1βproduction upon infec-tion with T.schoenleinii strain isolated from Tinea favosa patients,and rapid IL-1βsecretion from THP-1 cells was observed.Moreover,applying competitive inhibitors and gene specifi c silencing with shRNA,we found that T.sch-oenleinii induced IL-1βsecretion,ASC pyroptosome for-mation as well as caspase-1 activation were all dependent on NLRP3.Cathepsin B activity,ROS production and K+effl ux were required for the infl ammasome activation by T.schoenleinii.Our data thus reveal that the NLRP3 infl am-masome plays an important role in host defense against T.schoenleinii,and suggest that manipulating NLRP3 signaling can be a novel approach for control of diseases caused by T.schoenleinii infection.

Translationally controlled tumor protein: the mediator promoting cancer invasion and migration and its potential clinical prospects

Translationally controlled tumor protein(TCTP) is a highly conserved multifunctional protein localized in the cytoplasm and nucleus of eukaryotic cells. It is secreted through exosomes and its degradation is associated with the ubiquitin-proteasome system(UPS), heat shock protein 27(Hsp27), and chaperone-mediated autophagy(CMA). Its structure contains three α-helices and eleven β-strands, and features a helical hairpin as its hallmark. TCTP shows a remarkable similarity to the methionine-R-sulfoxide reductase B(Msr B) and mammalian suppressor of Sec4(Mss4/Dss4) protein families, which exerts guanine nucleotide exchange factor(GEF) activity on small guanosine triphosphatase(GTPase) proteins, suggesting that some functions of TCTP may at least depend on its GEF action. Indeed, TCTP exerts GEF activity on Ras homolog enriched in brain(Rheb) to boost the growth and proliferation of Drosophila cells. TCTP also enhances the expression of cell division control protein 42 homolog(Cdc42) to promote cancer cell invasion and migration. Moreover, TCTP regulates cytoskeleton organization by interacting with actin microfilament(MF) and microtubule(MT) proteins and inducing the epithelial-mesenchymal transition(EMT) process. In essence, TCTP promotes cancer cell movement. It is usually highly expressed in cancerous tissues and thus reduces patient survival;meanwhile, drugs can target TCTP to reduce this effect. In this review, we summarize the mechanisms of TCTP in promoting cancer invasion and migration, and describe the current inhibitory strategy to target TCTP in cancerous diseases.