Blockade of endogenous B7-H1 suppresses antibacterial protection after primary Listeria monocytogenes infection
2008
Seo, Su-Kil | Jeong, Hye-young | Park, Sae-Gwang | Lee, Soo-Woong | Choi, Il-Whan | Chen, Lieping | Choi, Inhak
B7-H1 (also known as CD274 and PD-L1) is a cosignalling molecule regulating T-cell immunity positively or negatively in vivo. However, little is known about the role of endogenous B7-H1 in bacterial infection. We found that B7-H1 expression was up-regulated in various cell populations including CD4⁺ and CD8⁺ T cells, natural killer (NK) cells and macrophages following Listeria monocytogenes infection. Administration of the antagonistic B7-H1 monoclonal antibody resulted in a significant increase in mortality in mice infected with a lethal dose of L. monocytogenes compared with mice given the control immunoglobulin. In vivo blockade of B7-H1 greatly inhibited the production of tumour necrosis factor (TNF)-α and nitric oxide, key effector molecules responsible for intracellular killing by macrophages. B7-H1 blockade also suppressed the expression of granzyme B and interferon (IFN)-γ by NK cells. Interestingly, blocking of endogenous B7-H1 selectively inhibited CD8⁺ T cells rather than CD4⁺ T cells in response to L. monocytogenes infection, as evidenced by the reduction of IFN-γ production and the expression of effector surface markers including CD62Lint/low and CD44high in CD8⁺ T cells from mice given anti-B7-H1 monoclonal antibody. In addition, we found that the proliferation of listeriolysin-O (LLO)-specific and IFN-γ-producing L. monocytogenes-reactive CD8⁺ T cells was significantly decreased not only in the effector phase but also in the memory phase in the presence of anti-B7-H1 antibody. Our findings thus suggest that endogenous B7-H1 can provide positive costimulatory signals for innate and adaptive immunity leading to protection against intracellular bacterial infection.
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