title: Reduced apoptosis of mouse macrophages induced by yscW mutant of Yersinia pestis results from the reduced secretion of YopJ and relates to caspase-3 signal pathway.
abstract: The virulence of the pathogenic Yersinia species depends on a plasmid-encoded type III secretion system (T3SS) that injects six Yersinia outer protein (Yop) effector proteins into the cytosol of macrophages, leading to disruption of host defence mechanisms. Here, we report that a T3SS structural protein YscW of Yersinia pestis contributed to the induction of apoptosis of murine macrophages. The apoptotic percentage of macrophages, from both mouse peritoneal cavity and spleen, and of RAW264.7 cell line, caused by the yscW mutant strain was significantly lower than that by wild type (WT) Y. pestis and yscW complemented strain. Meanwhile, detection of caspase-3 activity in macrophages, a key apoptosis-inducing protein, showed coincident results with the changes of macrophage apoptosis induced by WT, yscW mutant and complemented strains, indicating that macrophage apoptosis was related to caspase-3 signal pathways. However, ectopic expression of YscW in RAW264.7 cells cannot increase the macrophage apoptosis and death, suggesting that YscW itself could not induce macrophage apoptosis directly. To get insight into the mechanism of this phenomenon, we investigated the secretion of YopJ, which has been thought to be the only Yop effector related to apoptosis, in WT, mutant and complemented strains, respectively. Results showed that in yscW mutant strain, secretion of YopJ was decreased significantly in the supernatant than that in WT or complemented strain. This means although YscW does not induce apoptosis directly, it can indirectly affect apoptosis through reducing the secretion of YopJ.
authors.affiliation: Laboratory of Analytical Microbiology, State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Bi
authors.forename: Z
authors.initials: Z
authors.lastname: Du
authors.forename: H
authors.initials: H
authors.lastname: Yang
authors.forename: Z
authors.initials: Z
authors.lastname: Guo
authors.forename: Y
authors.initials: Y
authors.lastname: Tan
authors.forename: Z
authors.initials: Z
authors.lastname: Zhu
authors.forename: Ruifu
authors.initials: R
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D008264:Macrophages / Q000166:cytology* / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000276:immunology; D051379:Mice; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology; D014162:Transfection; D014774:Virulence / Q000235:genetics / Q000276:immunology; D015010:Yersinia pestis / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; C078909:YopB protein, Yersinia; C078910:YopD protein, Yersinia; C109227:YopP protein, Yersinia; C060772:yopM protein, Yersinia; C505409:Casp3 protein, mouse; D053148:Caspase 3