4-1BB (CD137) is required for rapid clearance of Listeria monocytogenes infection.
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.
Lee
Sang-C
SC
Immunomodulation Research Center, University of Ulsan, San 29, Mukeo-dong, Nam-ku, Ulsan, Republic of Korea, 680-749.
Ju
Seong-A
SA
Pack
Ha-N
HN
Heo
Sook-K
SK
Suh
Jae-H
JH
Park
Sang-M
SM
Choi
Boem-K
BK
Kwon
Byoung S
BS
Kim
Byung S
BS
D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D006098:Granulocytes / Q000276:immunology; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology*; D008099:Liver / Q000166:cytology / Q000276:immunology; D051379:Mice; D009504:Neutrophils / Q000378:metabolism; D010587:Phagocytosis / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000172:deficiency / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor / Q000172:deficiency / Q000276:immunology*; D018805:Sepsis / Q000276:immunology; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9
D015703:Antigens, CD; D017382:Reactive Oxygen Species; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C505715:Tnfrsf9 protein, mouse; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D002118:Calcium