title: CD11c(+)  CD103(+) cells of Mycobacterium tuberculosis-infected C57BL/6 but not of BALB/c mice induce a high frequency of interferon-γ- or interleukin-17-producing CD4(+) cells.
abstract: The magnitude of the cellular adaptive immune response is critical for the control of Mycobacterium tuberculosis infection in the chronic phase. In addition, the genetic background is equally important for resistance or susceptibility to tuberculosis. In this study, we addressed whether lung populations of dendritic cells, obtained from genetically different hosts, would play a role in the magnitude and function of CD4(+) populations generated after M. tuberculosis infection. Thirty days post-infection, C57BL/6 mice, which generate a stronger interferon-γ (IFN-γ)-mediated immune response than BALB/c mice, exhibited a higher number and frequency of lung CD11c(+)  CD11b(-)  CD103(+) cells compared with BALB/c mice, which exhibited a high frequency of lung CD11c(+)  CD11b(+)  CD103(-) cells. CD11c(+)  CD11b(-)  CD103(+) cells, purified from lungs of infected C57BL/6 mice, but not from infected BALB/c mice, induced a higher frequency of IFN-γ-producing or interleukin-17 (IL-17)-producing CD4(+) cells. Moreover, CD4(+) cells also arrive at the lung of C57BL/6 mice faster than in BALB/c mice. This pattern of immune response seems to be associated with higher gene expression for CCL4, CCL19, CCL20 and CCR5 in the lungs of infected C57BL/6 mice compared with infected BALB/c mice. The results described here show that the magnitude of IFN-γ-producing or IL-17-producing CD4(+) cells is dependent on CD11c(+)  CD11b(-)  CD103(+) cells, and this pattern of immune response is directly associated with the host genetic background. Therefore, differences in the genetic background contribute to the identification of immunological biomarkers that can be used to design human assays to predict progression of M. tuberculosis infection.
authors.affiliation: Department of Biochemistry and Immunology, Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: Cássia A
authors.initials: CA
authors.lastname: Sérgio
authors.forename: Thais B
authors.initials: TB
authors.lastname: Bertolini
authors.forename: Ana Flávia
authors.initials: AF
authors.lastname: Gembre
authors.forename: Rafael Q
authors.initials: RQ
authors.lastname: Prado
authors.forename: Vânia L D
authors.initials: VL
authors.lastname: Bonato
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D039481:CD11b Antigen / Q000276:immunology / Q000378:metabolism; D039521:CD11c Antigen / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D004195:Disease Models, Animal; D005260:Female; D005838:Genotype; D007111:Immunity, Cellular; D039001:Integrin alpha Chains / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D010641:Phenotype; D015398:Signal Transduction; D013045:Species Specificity; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D013997:Time Factors; D014397:Tuberculosis, Pulmonary / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology
chemical_list: D015703:Antigens, CD; D039481:CD11b Antigen; D039521:CD11c Antigen; D039001:Integrin alpha Chains; D020381:Interleukin-17; C091367:alpha E integrins; D007371:Interferon-gamma
keywords: T helper type 1 cells; T helper type 17 cells; dendritic cells; genetic background; tuberculosis