title: Cell-to-cell transfer of M. tuberculosis antigens optimizes CD4 T cell priming.
abstract: During Mycobacterium tuberculosis and other respiratory infections, optimal T cell activation requires pathogen transport from the lung to a local draining lymph node (LN). However, the infected inflammatory monocyte-derived dendritic cells (DCs) that transport M. tuberculosis to the local lymph node are relatively inefficient at activating CD4 T cells, possibly due to bacterial inhibition of antigen presentation. We found that infected migratory DCs release M. tuberculosis antigens as soluble, unprocessed proteins for uptake and presentation by uninfected resident lymph node DCs. This transfer of bacterial proteins from migratory to local DCs results in optimal priming of antigen-specific CD4 T cells, which are essential in controlling tuberculosis. Additionally, this mechanism does not involve transfer of the whole bacterium and is distinct from apoptosis or exosome shedding. These findings reveal a mechanism that bypasses pathogen inhibition of antigen presentation by infected cells and generates CD4 T cell responses that control the infection.
authors.affiliation: Division of Infectious Diseases and Immunology, Department of Medicine, New York University School of Medicine, New York, NY 10016, USA.
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 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 / Q000378:metabolism*; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000382:microbiology*; D003713:Dendritic Cells / Q000382:microbiology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D054884:Host-Pathogen Interactions; D008168:Lung / Q000382:microbiology; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008817:Mice, Mutant Strains; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000472:pathogenicity*
chemical_list: D000942:Antigens, Bacterial; D000949:Histocompatibility Antigens Class II; C072681:Mycobacterium tuberculosis antigens