title: Differentiation of human mononuclear phagocytes increases their innate response to Mycobacterium tuberculosis infection.
abstract: The heterogeneity of mononuclear phagocytes, partially explained by cell differentiation, influences the activation of innate responses. It has been reported that Mycobacterium tuberculosis inhibits monocyte differentiation into either dendritic cells or macrophages. To evaluate whether the activation of effector mechanisms against M. tuberculosis differ between less and more differentiated mononuclear phagocytes, we compared monocytes differentiated in vitro for 24 h (MON24) and 120 h (MDM120) infected with M. tuberculosis H37Rv, H37Ra and the clinical isolate UT127 at different multiplicity of infection. MDM120 phagocytosed more M. tuberculosis, inhibited mycobacterial growth and did not die in response to the infection, compared with MON24. In contrast, MON24 become Annexin V and Propidium iodide positive after 36 h of M. tuberculosis infection. Although, there were striking differences between MON24 and MDM120, there were also some differences in the response to the mycobacterial strains used. Finally, in MDM120 infected with M. tuberculosis H37Rv, a lower percentage of mycobacterial phagosomes accumulated transferrin and a higher percentage co-localized with cathelicidin than in MON24. These results demonstrate that innate responses induced by M. tuberculosis depends upon the stage of differentiation of mononuclear phagocytes and support that terminally differentiated cells are more efficient anti-mycobacterial effectors than the less differentiated ones.
authors.affiliation: Grupo de Inmunología Celular e Inmunogenética, Instituto de Investigaciones Médicas, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia; Centro Colombiano de Investigación en Tuberculosis, Medellín, Colombia. Electronic address: dmcastano@gmail.com.
authors.forename: Diana
authors.initials: D
authors.lastname: Castaño
authors.affiliation: Grupo de Inmunología Celular e Inmunogenética, Instituto de Investigaciones Médicas, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia; Centro Colombiano de Investigación en Tuberculosis, Medellín, Colombia. Electronic address: lfgarcia@udea.edu.co.
authors.forename: Luis F
authors.initials: LF
authors.lastname: García
authors.affiliation: Grupo de Inmunología Celular e Inmunogenética, Instituto de Investigaciones Médicas, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia; Unidad de Citometría de Flujo, Sede de Investigación Universitaria, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia; Centro Colombiano de Investigación en Tuberculosis, Medellín, Colombia. Electronic address: mrojaslop@hotmail.com.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Rojas
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D016923:Cell Death / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007113:Immunity, Innate / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D008863:Microspheres; D009169:Mycobacterium tuberculosis / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D011971:Receptors, Immunologic / Q000378:metabolism; D014376:Tuberculosis / Q000276:immunology* / Q000473:pathology; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D016207:Cytokines; D011971:Receptors, Immunologic; C028495:phagocytosis receptor; D006861:Hydrogen Peroxide; D054804:Cathelicidins
keywords: Differentiation; Macrophage; Monocyte; Mononuclear phagocyte; Mycobacterium tuberculosis; Phagocyte heterogeneity