title: Blockade of endogenous B7-H1 suppresses antibacterial protection after primary Listeria monocytogenes infection.
abstract: 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)-alpha 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)-gamma 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-gamma production and the expression of effector surface markers including CD62L(int/low) and CD44(high) 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-gamma-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.
authors.affiliation: Department of Microbiology, and Bio-Marker Research Center for Personalized Therapy, College of Medicine, Inje University, Busan, Republic of Korea.
authors.forename: Su-Kil
authors.initials: SK
authors.lastname: Seo
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Jeong
authors.forename: Sae-Gwang
authors.initials: SG
authors.lastname: Park
authors.forename: Soo-Woong
authors.initials: SW
authors.lastname: Lee
authors.forename: Il-Whan
authors.initials: IW
authors.lastname: Choi
authors.forename: Lieping
authors.initials: L
authors.lastname: Chen
authors.forename: Inhak
authors.initials: I
authors.lastname: Choi
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology* / Q000378:metabolism; D060890:B7-H1 Antigen; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D015169:Colony Count, Microbial; D007108:Immune Tolerance / Q000276:immunology*; D007111:Immunity, Cellular; D007113:Immunity, Innate; D008088:Listeriosis / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D008562:Membrane Glycoproteins; D010455:Peptides