title: Antigen Export Reduces Antigen Presentation and Limits T Cell Control of M. tuberculosis.
abstract: Persistence of Mycobacterium tuberculosis results from bacterial strategies that manipulate host adaptive immune responses. Infected dendritic cells (DCs) transport M. tuberculosis to local lymph nodes but activate CD4 T cells poorly, suggesting bacterial manipulation of antigen presentation. However, M. tuberculosis antigens are also exported from infected DCs and taken up and presented by uninfected DCs, possibly overcoming this blockade of antigen presentation by infected cells. Here we show that the first stage of this antigen transfer, antigen export, benefits M. tuberculosis by diverting bacterial proteins from the antigen presentation pathway. Kinesin-2 is required for antigen export and depletion of this microtubule-based motor increases activation of antigen-specific CD4 T cells by infected cells and improves control of intracellular infection. Thus, although antigen transfer enables presentation by bystander cells, it does not compensate for reduced antigen presentation by infected cells and represents a bacterial strategy for CD4 T cell evasion.
authors.affiliation: Division of Infectious Diseases and Immunology, Department of Medicine, New York University School of Medicine, New York, NY 10016, USA; Department of Pathology, New York University School of Medicine, New York, NY 10016, USA. Electronic address: smiats@gmail.com.
authors.forename: Smita
authors.initials: S
authors.lastname: Srivastava
authors.affiliation: Division of Infectious Diseases and Immunology, Department of Medicine, New York University School of Medicine, New York, NY 10016, USA; Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Grace
authors.affiliation: Division of Infectious Diseases and Immunology, Department of Medicine, New York University School of Medicine, New York, NY 10016, USA; Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA; Department of Pathology, New York University School of Medicine, New York, NY 10016, USA. Electronic address: joel.ernst@med.nyu.edu.
authors.forename: Joel D
authors.initials: JD
authors.lastname: Ernst
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D021381:Protein Transport; D014376:Tuberculosis / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology
chemical_list: D000942:Antigens, Bacterial; C072681:Mycobacterium tuberculosis antigens