title: A BTLA-mediated bait and switch strategy permits Listeria expansion in CD8α(+) DCs to promote long-term T cell responses.
abstract: Listeria monocytogenes infected CD8α(+) DCs in the spleen are essential for CD8(+) T cell generation. CD8α(+) DCs are also necessary for Listeria expansion and dissemination within the host. The mechanisms that regulate CD8α(+) DCs to allow Listeria expansion are unclear. We find that activating the B and T lymphocyte attenuator (BTLA), a coinhibitory receptor for T cells, suppresses, while blocking BTLA enhances, both the primary and memory CD8 T cell responses against Listeria. Btla(-/-) mice have lower effector and memory CD8(+) T cells while paradoxically also being more resistant to Listeria. Although bacterial entry into Btla(-/-) CD8α(+) DCs is unaffected, Listeria fails to expand within these cells. BTLA signaling limits Fas/FasL-mediated suppression of Listeria expansion within CD8α(+) DCs to more effectively alert adaptive immune cells. This study uncovers a BTLA-mediated strategy used by the host that permits Listeria proliferation to enable increasing T cell responses for long-term protection.
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Xuanming
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL 60637, USA; International joint Cancer Institute, The Second Military Medical University, Shanghai, 200433, China.
authors.forename: Xunmin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Yonglian
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Tony
authors.initials: T
authors.lastname: Tu
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: May Lynne
authors.initials: ML
authors.lastname: Fu
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL 60637, USA. Electronic address: mendy.miller@gmail.com.
authors.forename: Mendy
authors.initials: M
authors.lastname: Miller
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL 60637, USA. Electronic address: yfu@uchicago.edu.
authors.forename: Yang-Xin
authors.initials: YX
authors.lastname: Fu
mesh_terms: D000818:Animals; D016827:CD8 Antigens / Q000032:analysis*; D003713:Dendritic Cells / Q000737:chemistry / Q000276:immunology* / Q000382:microbiology*; D054884:Host-Pathogen Interactions; D008089:Listeria monocytogenes / Q000254:growth & development / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D011971:Receptors, Immunologic / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: C488868:BTLA protein, mouse; D016827:CD8 Antigens; D011971:Receptors, Immunologic