title: Salmonella impairs CD8 T cell response through PD-1: PD-L axis.
abstract: We have shown that Salmonella remains for a long period of time within B cells, plasma cells, and bone marrow B cell precursors, which might allow persistence and dissemination of infection. Nonetheless, how infected cells evade CD8 T cell response has not been characterized. Evidence indicates that some pathogens exploit the PD-1: PD-L (PD-L1 and PD-L2) interaction to inhibit CD8 T cells response to contribute the chronicity of the infection. To determine whether the PD-1: PD-L axis plays a role during Salmonella infection; we evaluated PD-1 expression in antigen-specific CD8 T cells and PD-1 ligands in Salmonella-infected cells. Our results show that infected B cells and macrophages express continuously co-stimulatory (CD40, CD80, and CD86) and inhibitory molecules (PD-L1 and PD-L2) in early and late stages of chronic Salmonella infection, while antigen-specific CD8 T cells express in a sustained manner PD-1 in the late stages of infection. Blocking this axis restores the ability of the CD8 T cells to proliferate and eliminate primary infected APCs. Therefore, a continuous PD-1: PDL interaction might be a mechanism employed by Salmonella to negatively regulate Salmonella-specific CD8 T cell cytotoxic response in order to remain within the host for a long period of time.
authors.affiliation: Departamento de Biomedicina Molecular, Centro de Investigación y Estudios Avanzados del IPN, México City CP 07360, Mexico.
authors.forename: Marcela
authors.initials: M
authors.lastname: López-Medina
authors.affiliation: Departamento de Biomedicina Molecular, Centro de Investigación y Estudios Avanzados del IPN, México City CP 07360, Mexico.
authors.forename: Ismael
authors.initials: I
authors.lastname: Carrillo-Martín
authors.affiliation: Departamento de Biomedicina Molecular, Centro de Investigación y Estudios Avanzados del IPN, México City CP 07360, Mexico; Doctorado en Ciencias Biomédicas, Facultad de Medicina, UNAM, Mexico City CP 045510, Mexico.
authors.forename: Jessica
authors.initials: J
authors.lastname: Leyva-Rangel
authors.affiliation: Instituto Nacional de Salud Pública, Secretaría de Salud y Asistencia, Cuernavaca, Morelos CP 62100, Mexico.
authors.forename: Celia
authors.initials: C
authors.lastname: Alpuche-Aranda
authors.affiliation: Departamento de Biomedicina Molecular, Centro de Investigación y Estudios Avanzados del IPN, México City CP 07360, Mexico. Electronic address: vortiz@cinvestav.mx.
authors.forename: Vianney
authors.initials: V
authors.lastname: Ortiz-Navarrete
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D060890:B7-H1 Antigen / Q000378:metabolism; D015415:Biomarkers; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D016130:Immunophenotyping; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D008822:Mice, Transgenic; D010641:Phenotype; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000378:metabolism; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012475:Salmonella / Q000276:immunology* / Q000472:pathogenicity; D012480:Salmonella Infections / Q000276:immunology* / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000276:immunology; D015398:Signal Transduction; D014774:Virulence / Q000276:immunology
chemical_list: D060890:B7-H1 Antigen; D015415:Biomarkers; D008024:Ligands; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor
keywords: CD8 T cells; Infection; PD-1; PD-L1