4-1BB (CD137) Is Required for Rapid Clearance of Listeria monocytogenes Infection

• Published in: Infection and Immunity 2005-08, Vol.73 (8), p.5144-5151
• Main Authors: Lee, Sang-C, Ju, Seong-A, Pack, Ha-N, Heo, Sook-K, Suh, Jae-H, Park, Sang-M, Choi, Boem-K, Kwon, Byoung S, Kim, Byung S
• Format: Article
• Language: English
• Subjects: Animals; Antigens, CD - immunology; Bacteriology; Biological and medical sciences; Calcium - metabolism; Fundamental and applied biological sciences. Psychology; Granulocytes - immunology; Host Response and Inflammation; Listeria monocytogenes; Listeria monocytogenes - immunology; Listeriosis - immunology; Liver - cytology; Liver - immunology; Mice; Microbiology; Miscellaneous; Neutrophils - metabolism; Phagocytosis - physiology; Reactive Oxygen Species - metabolism; Receptors, Nerve Growth Factor - deficiency; Receptors, Nerve Growth Factor - immunology; Receptors, Tumor Necrosis Factor - deficiency; Receptors, Tumor Necrosis Factor - immunology; Sepsis - immunology; Tumor Necrosis Factor Receptor Superfamily, Member 9
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/iai.73.8.5144-5151.2005

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[superscript -/-]) mice are much more susceptible to Listeria monocytogenes (intracellular bacteria) infections than wild-type mice. Upon L. monocytogenes infection, 4-1BB[superscript -/-] mice showed a lower survival rate, a higher bacterial burden in organs, and larger hepatic microabscesses than 4-1BB[superscript +/+] mice. 4-1BB[superscript -/-] mice also had impairment in clearance of bacteria from the bloodstream. Neutrophils from 4-1BB[superscript +/+] mice constitutively expressed 4-1BB, which could be activated to induce intracellular Ca²⁺ influx by ligation with anti-4-1BB antibody. On the other hand, neutrophils from 4-1BB[superscript -/-] mice were defective in reactive oxygen species generation, phagocytic activities, and intracellular Ca²⁺ 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.