title: Diverging biological roles among human monocyte subsets in the context of tuberculosis infection.
abstract: Circulating monocytes (Mo) play an essential role in the host immune response to chronic infections. We previously demonstrated that CD16(pos) Mo were expanded in TB (tuberculosis) patients, correlated with disease severity and were refractory to dendritic cell differentiation. In the present study, we investigated whether human Mo subsets (CD16(neg) and CD16(pos)) differed in their ability to influence the early inflammatory response against Mycobacterium tuberculosis. We first evaluated the capacity of the Mo subsets to migrate and engage a microbicidal response in vitro. Accordingly, CD16(neg) Mo were more prone to migrate in response to different mycobacteria-derived gradients, were more resistant to M. tuberculosis intracellular growth and produced higher reactive oxygen species than their CD16(pos) counterpart. To assess further the functional dichotomy among the human Mo subsets, we carried out an in vivo analysis by adapting a hybrid mouse model (SCID/Beige, where SCID is severe combined immunodeficient) to transfer each Mo subset, track their migratory fate during M. tuberculosis infection, and determine their impact on the host immune response. In M. tuberculosis-infected mice, the adoptively transferred CD16(neg) Mo displayed a higher lung migration index, induced a stronger pulmonary infiltration of murine leucocytes expressing pro- and anti-inflammatory cytokines, and significantly decreased the bacterial burden, in comparison with CD16(pos) Mo. Collectively, our results indicate that human Mo subsets display divergent biological roles in the context of M. tuberculosis infection, a scenario in which CD16(neg) Mo may contribute to the anti-mycobacterial immune response, whereas CD16(pos) Mo might promote microbial resilience, shedding light on a key aspect of the physiopathology of TB disease.
authors: *Institute of Experimental Medicine-CONICET, National Academy of Medicine, Pacheco de Melo 3081 (1425), Buenos Aires, Argentina.
authors: Luciana
authors: L
authors: Balboa
authors: †Department of Experimental Pathology, National Institute of Medical Sciences & Nutrition "Salvador Zubirán", Vasco de Quiroga 15, Sección 16, Delegación Tlalpan (14000), Mexico City, Mexico.
authors: Jorge
authors: J
authors: Barrios-Payan
authors: ‡Department of Molecular Biomedicine, Center for Research and Advances Studies, National Polytechnic Institute, Av. Instituto Politécnico Nacional 2508, Gustavo A. Madero, San Pedro Zacatenco (07360), Mexico City, Mexico.
authors: Erika
authors: E
authors: González-Domínguez
authors: §CNRS, Institut de Pharmacologie et de Biologie Structurale, 205 route de Narbonne (31077), Toulouse, France.
authors: Claire
authors: C
authors: Lastrucci
authors: §CNRS, Institut de Pharmacologie et de Biologie Structurale, 205 route de Narbonne (31077), Toulouse, France.
authors: Geanncarlo
authors: G
authors: Lugo-Villarino
authors: †Department of Experimental Pathology, National Institute of Medical Sciences & Nutrition "Salvador Zubirán", Vasco de Quiroga 15, Sección 16, Delegación Tlalpan (14000), Mexico City, Mexico.
authors: Dulce
authors: D
authors: Mata-Espinoza
authors: *Institute of Experimental Medicine-CONICET, National Academy of Medicine, Pacheco de Melo 3081 (1425), Buenos Aires, Argentina.
authors: Pablo
authors: P
authors: Schierloh
authors: *Institute of Experimental Medicine-CONICET, National Academy of Medicine, Pacheco de Melo 3081 (1425), Buenos Aires, Argentina.
authors: Denise
authors: D
authors: Kviatcovsky
authors: §CNRS, Institut de Pharmacologie et de Biologie Structurale, 205 route de Narbonne (31077), Toulouse, France.
authors: Olivier
authors: O
authors: Neyrolles
authors: §CNRS, Institut de Pharmacologie et de Biologie Structurale, 205 route de Narbonne (31077), Toulouse, France.
authors: Isabelle
authors: I
authors: Maridonneau-Parini
authors: ‡Department of Molecular Biomedicine, Center for Research and Advances Studies, National Polytechnic Institute, Av. Instituto Politécnico Nacional 2508, Gustavo A. Madero, San Pedro Zacatenco (07360), Mexico City, Mexico.
authors: Carmen
authors: C
authors: Sánchez-Torres
authors: *Institute of Experimental Medicine-CONICET, National Academy of Medicine, Pacheco de Melo 3081 (1425), Buenos Aires, Argentina.
authors: María del Carmen
authors: Mdel C
authors: Sasiain
authors: †Department of Experimental Pathology, National Institute of Medical Sciences & Nutrition "Salvador Zubirán", Vasco de Quiroga 15, Sección 16, Delegación Tlalpan (14000), Mexico City, Mexico.
authors: Rogelio
authors: R
authors: Hernández-Pando
mesh_terms: D000818:Animals; D058491:Bacterial Load; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D004195:Disease Models, Animal; D058851:GPI-Linked Proteins / Q000276:immunology / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D016513:Mice, SCID; D009000:Monocytes / Q000145:classification / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000637:transplantation; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism; D016897:Respiratory Burst; D013997:Time Factors; D014397:Tuberculosis, Pulmonary / Q000097:blood / Q000276:immunology* / Q000382:microbiology
chemical_list: C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D017382:Reactive Oxygen Species; D017452:Receptors, IgG