title: The Mannose Receptor Is Involved in the Phagocytosis of Mycobacteria-Induced Apoptotic Cells.
abstract: Upon Mycobacterium tuberculosis infection, macrophages may undergo apoptosis, which has been considered an innate immune response. The pathways underlying the removal of dead cells in homeostatic apoptosis have been extensively studied, but little is known regarding how cells that undergo apoptotic death during mycobacterial infection are removed. This study shows that macrophages induced to undergo apoptosis with mycobacteria cell wall proteins are engulfed by J-774A.1 monocytic cells through the mannose receptor. This demonstration was achieved through assays in which phagocytosis was inhibited with a blocking anti-mannose receptor antibody and with mannose receptor competitor sugars. Moreover, elimination of the mannose receptor by a specific siRNA significantly diminished the expression of the mannose receptor and the phagocytosis of apoptotic cells. As shown by immunofluorescence, engulfed apoptotic bodies are initially located in Rab5-positive phagosomes, which mature to express the phagolysosome marker LAMP1. The phagocytosis of dead cells triggered an anti-inflammatory response with the production of TGF-β and IL-10 but not of the proinflammatory cytokines IL-12 and TNF-α. This study documents the previously unreported participation of the mannose receptor in the removal of apoptotic cells in the setting of tuberculosis (TB) infection. The results challenge the idea that apoptotic cell phagocytosis in TB has an immunogenic effect.
authors.affiliation: Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, 04510 México City, DF, Mexico.
authors.forename: Teresa
authors.identifier: 0000-0002-4518-7513
authors.initials: T
authors.lastname: Garcia-Aguilar
authors.affiliation: Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, 04510 México City, DF, Mexico.
authors.forename: Patricia
authors.identifier: 0000-0001-6578-959X
authors.initials: P
authors.lastname: Espinosa-Cueto
authors.affiliation: Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, 04510 México City, DF, Mexico.
authors.forename: Alejandro
authors.identifier: 0000-0001-9679-4949
authors.initials: A
authors.lastname: Magallanes-Puebla
authors.affiliation: Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, 04510 México City, DF, Mexico.
authors.forename: Raúl
authors.identifier: 0000-0002-5752-8995
authors.initials: R
authors.lastname: Mancilla
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D002473:Cell Wall / Q000276:immunology*; D000067128:Extracellular Vesicles / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics / Q000502:physiology*; D051907:Lysosomal Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D009000:Monocytes / Q000276:immunology*; D020102:Mycobacterium smegmatis / Q000254:growth & development / Q000276:immunology*; D010587:Phagocytosis; D010588:Phagosomes / Q000276:immunology / Q000648:ultrastructure; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D020696:rab5 GTP-Binding Proteins / Q000032:analysis; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D016753:Interleukin-10; D018664:Interleukin-12; D037181:Lectins, C-Type; D051907:Lysosomal Membrane Proteins; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D020696:rab5 GTP-Binding Proteins; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1