title: Monocyte-derived dendritic cells early exposed to Mycobacterium tuberculosis induce an enhanced T helper 17 response and transfer mycobacterial antigens.
abstract: Tuberculosis (TB) is a complex disease, and the success of the bacterium depends on its ability to evade the immune response. Previously, we determined that Mycobacterium tuberculosis (Mtb) impairs the function of dendritic cells (DC), promoting the generation of cells that are poor stimulators of mycobacterial antigen-specific CD4T cells, which are required to control this persistent infection. In this study, we aimed to determine the mechanisms by which monocyte-derived DCs differentiated in the presence of Mtb (MtbDC) may impact on the proliferation of specific anti-mycobacterial T cells. We found that the presence of Mtb during monocyte-derived DC differentiation favours T helper (Th) 2 and Th17 polarization, in detriment of a Th1 response, compared to DC mature with Mtb. The bias on T cell polarization was associated to the profile of C-type lectin receptors expression found in MtbDC (DC-SIGNlow/MRlow/Dectin-1high). Alternatively, MtbDC release Mtb antigens (Ag) that can be taken up and presented by bystander DC, promoting the proliferation of CD4T cells, but to a lesser extent than direct presentation by Mtb-matured DC. In summary, we have further characterized the generation of MtbDC as an effective evasion strategy driven by the pathogen, leading to the inhibition of Ag-presentation and bias of T cell polarization towards Th2 and Th17 profiles, features which partially explain the persistence of Mtb in the host.
authors.affiliation: Institute of Experimental Medicine-CONICET, National Academy of Medicine, Pacheco de Melo 3081, 1425 Buenos Aires, Argentina. Electronic address: luciana_balboa@hotmail.com.
authors.forename: Luciana
authors.initials: L
authors.lastname: Balboa
authors.affiliation: Institute of Experimental Medicine-CONICET, National Academy of Medicine, Pacheco de Melo 3081, 1425 Buenos Aires, Argentina. Electronic address: denise.kv@hotmail.com.
authors.forename: Denise
authors.initials: D
authors.lastname: Kviatcovsky
authors.affiliation: Institute of Experimental Medicine-CONICET, National Academy of Medicine, Pacheco de Melo 3081, 1425 Buenos Aires, Argentina. Electronic address: lp_shier@hotmail.com.
authors.forename: Pablo
authors.initials: P
authors.lastname: Schierloh
authors.affiliation: Institute of Experimental Medicine-CONICET, National Academy of Medicine, Pacheco de Melo 3081, 1425 Buenos Aires, Argentina. Electronic address: marinagarcia.ar@hotmail.com.
authors.forename: Marina
authors.initials: M
authors.lastname: García
authors.affiliation: Institute of Experimental Medicine-CONICET, National Academy of Medicine, Pacheco de Melo 3081, 1425 Buenos Aires, Argentina. Electronic address: sildelabar@gmail.com.
authors.forename: Silvia
authors.initials: S
authors.lastname: de la Barrera
authors.affiliation: Institute of Experimental Medicine-CONICET, National Academy of Medicine, Pacheco de Melo 3081, 1425 Buenos Aires, Argentina. Electronic address: msasiain@hematologia.anm.edu.ar.
authors.forename: María Del Carmen
authors.initials: MDC
authors.lastname: Sasiain
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology* / Q000378:metabolism*; D001782:Blood Donors; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D064368:Healthy Volunteers; D006801:Humans; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial
keywords: Antigens transfer; Bacterial infection; Dendritic cells; Mycobacterium infections; Pulmonary; Tuberculosis