| First Author | Vázquez-Torres A | Year | 2001 |
| Journal | Proc Natl Acad Sci U S A | Volume | 98 |
| Issue | 5 | Pages | 2561-5 |
| PubMed ID | 11226278 | Mgi Jnum | J:126397 |
| Mgi Id | MGI:3761207 | Doi | 10.1073/pnas.041618998 |
| Citation | Vazquez-Torres A, et al. (2001) Defective localization of the NADPH phagocyte oxidase to Salmonella-containing phagosomes in tumor necrosis factor p55 receptor-deficient macrophages. Proc Natl Acad Sci U S A 98(5):2561-5 |
| abstractText | Tumor necrosis factor receptor (TNFR) p55-knockout (KO) mice are susceptible profoundly to Salmonella infection. One day after peritoneal inoculation, TNFR-KO mice harbor 1,000-fold more bacteria in liver and spleen than wild-type mice despite the formation of well organized granulomas. Macrophages from TNFR-KO mice produce abundant quantities of reactive oxygen and nitrogen species in response to Salmonella but nevertheless exhibit poor bactericidal activity. Treatment with IFN-gamma enhances killing by wild-type macrophages but does not restore the killing defect of TNFR-KO cells. Bactericidal activity of macrophages can be abrogated by a deletion in the gene encoding TNFalpha but not by saturating concentrations of TNF-soluble receptor, suggesting that intracellular TNFalpha can regulate killing of Salmonella by macrophages. Peritoneal macrophages from TNFR-KO mice fail to localize NADPH oxidase-containing vesicles to Salmonella-containing vacuoles. A TNFR-KO mutation substantially restores virulence to an attenuated mutant bacterial strain lacking the type III secretory system encoded by Salmonella pathogenicity island 2 (SPI2), suggesting that TNFalpha and SPI2 have opposing actions on a common pathway of vesicular trafficking. TNFalpha-TNFRp55 signaling plays a critical role in the immediate innate immune response to an intracellular pathogen by optimizing the delivery of toxic reactive oxygen species to the phagosome. |
