title: B and T lymphocyte attenuator tempers early infection immunity.
abstract: Coinhibitory pathways are thought to act in later stages of an adaptive immune response, but whether coinhibition contributes to early innate immunity is unclear. We show that engagement of the newly discovered coinhibitory receptor B and T lymphocyte attenuator (BTLA) by herpesvirus entry mediator (HVEM) is critical for negatively regulating early host immunity against intracellular bacteria. Both HVEM(-/-) and BTLA(-/-), but not LIGHT(-/-), mice are more resistant to listeriosis compared with wild-type mice, and blockade of the BTLA pathway promotes, while engagement inhibits, early bacterial clearance. Differences in bacterial clearance were seen as early as 1 day postinfection, implicating the initial innate response. Therefore, innate cell function in BTLA(-/-) mice was studied. We show that innate cells from BTLA(-/-) mice secrete significantly more proinflammatory cytokines upon stimulation with heat-killed Listeria. These results provide the first evidence that a coinhibitory pathway plays a critical role in regulating early host innate immunity against infection.
authors: Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
authors: Yonglian
authors: Y
authors: Sun
authors: Nicholas K
authors: NK
authors: Brown
authors: Matthew J
authors: MJ
authors: Ruddy
authors: Mendy L
authors: ML
authors: Miller
authors: Youjin
authors: Y
authors: Lee
authors: Yang
authors: Y
authors: Wang
authors: Kenneth M
authors: KM
authors: Murphy
authors: Klaus
authors: K
authors: Pfeffer
authors: Lieping
authors: L
authors: Chen
authors: Jonathan
authors: J
authors: Kaye
authors: Yang-Xin
authors: YX
authors: Fu
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000276:immunology*; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D007113:Immunity, Innate / Q000276:immunology*; D008087:Listeria / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding / Q000276:immunology; D011971:Receptors, Immunologic / Q000172:deficiency / Q000276:immunology* / Q000378:metabolism; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000172:deficiency / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
chemical_list: C488868:BTLA protein, mouse; D016207:Cytokines; D011971:Receptors, Immunologic; D053240:Receptors, Tumor Necrosis Factor, Member 14