First Author | Lee SC | Year | 2005 |
Journal | Infect Immun | Volume | 73 |
Issue | 8 | Pages | 5144-51 |
PubMed ID | 16041031 | Mgi Jnum | J:100420 |
Mgi Id | MGI:3588471 | Doi | 10.1128/IAI.73.8.5144-5151.2005 |
Citation | Lee SC, et al. (2005) 4-1BB (CD137) is required for rapid clearance of Listeria monocytogenes infection. Infect Immun 73(8):5144-51 |
abstractText | 4-1BB (CD137), a member of the tumor necrosis factor receptor superfamily, is a T-cell-costimulatory receptor that is expressed on activated T cells, dendritic cells, and NK cells. Little has been reported about its role in early host defense against bacterial infection. In this study, we report that 4-1BB-deficient (4-1BB(-/-)) mice are much more susceptible to Listeria monocytogenes (intracellular bacteria) infections than wild-type mice. Upon L. monocytogenes infection, 4-1BB(-/-) mice showed a lower survival rate, a higher bacterial burden in organs, and larger hepatic microabscesses than 4-1BB(+/+) mice. 4-1BB(-/-) mice also had impairment in clearance of bacteria from the bloodstream. Neutrophils from 4-1BB(+/+) mice constitutively expressed 4-1BB, which could be activated to induce intracellular Ca(2+) influx by ligation with anti-4-1BB antibody. On the other hand, neutrophils from 4-1BB(-/-) mice were defective in reactive oxygen species generation, phagocytic activities, and intracellular Ca(2+) mobilization. In addition, mice pretreated with anti-4-1BB monoclonal antibody were much more resistant to L. monocytogenes infection than control antibody-treated mice. Our results support the notion that 4-1BB may play a major role in host defense against intracellular pathogens through neutrophil activation. |