title: Expression pattern of transcription factors and intracellular cytokines reveals that clinically cured tuberculosis is accompanied by an increase in Mycobacterium-specific Th1, Th2, and Th17 cells.
abstract: Tuberculosis (TB) remains a major global health problem and is the second biggest cause of death by infectious disease worldwide. Here, we investigate in vitro the Th1, Th2, Th17, and Treg cytokines and transcriptional factors produced after Mycobacterium-specific antigen stimulation in patients with active pulmonary tuberculosis, clinically cured pulmonary tuberculosis, and healthy donors with a positive tuberculin skin test (TST+). Together, our data indicate that clinical cure after treatment increases the percentages of Mycobacterium-specific Th1, Th2, and Th17 cells compared with those found in active-TB and TST+ healthy donors. These results show that the host-parasite equilibrium in latent TB breaks in favor of the microorganism and that the subsequent clinical recovery posttreatment does not return the percentage levels of such cells to those observed in latent tuberculosis. Additionally, our results indicate that rather than showing an increase in the percentage of Mycobacterium-specific Tregs, active-TB patients display lower Th1 : Treg and Th17 : Treg ratios. These data, together with lower Th1 : Th2 and Th17 : Th2 ratios, may indicate a mechanism by which the breakdown of the host-parasite equilibrium leads to active-TB and changes in the repertoire of Mycobacterium-specific Th cells that are associated with clinical cure after treatment of pulmonary tuberculosis.
authors.affiliation: Laboratory of Immunology, Institute of Biological Sciences, Triângulo Mineiro Federal University, 38025-180 Uberaba, MG, Brazil.
authors.forename: Marcos V
authors.initials: MV
authors.lastname: da Silva
authors.affiliation: Laboratory of Immunology, Institute of Biological Sciences, Triângulo Mineiro Federal University, 38025-180 Uberaba, MG, Brazil.
authors.forename: Vladimir J
authors.initials: VJ
authors.lastname: Massaro Junior
authors.affiliation: Laboratory of Immunology, Institute of Biological Sciences, Triângulo Mineiro Federal University, 38025-180 Uberaba, MG, Brazil ; Department of Pathology, Institute of Tropical Pathology and Public Health, Federal University of Goiás, 74605-050 Goiania, GO, Brazil.
authors.forename: Juliana R
authors.initials: JR
authors.lastname: Machado
authors.affiliation: Laboratory of Immunology, Institute of Biological Sciences, Triângulo Mineiro Federal University, 38025-180 Uberaba, MG, Brazil.
authors.forename: Djalma A A
authors.initials: DA
authors.lastname: Silva
authors.affiliation: Laboratory of Immunology, Institute of Biological Sciences, Triângulo Mineiro Federal University, 38025-180 Uberaba, MG, Brazil ; Human Immunology Research and Education Group (GEPIH), Technical School of Health, Federal University of Paraíba, 58051-900 João Pessoa, PB, Brazil.
authors.forename: Lúcio R
authors.initials: LR
authors.lastname: Castellano
authors.affiliation: Municipal Secretary Office of Health, 38065-160 Uberaba, MG, Brazil.
authors.forename: Patricia B D
authors.initials: PB
authors.lastname: Alexandre
authors.affiliation: Laboratory of Immunology, Institute of Biological Sciences, Triângulo Mineiro Federal University, 38025-180 Uberaba, MG, Brazil ; Laboratory of Biopathology and Molecular Biology, University of Uberaba, 38055-500 Uberaba, MG, Brazil.
authors.forename: Denise B R
authors.initials: DB
authors.lastname: Rodrigues
authors.affiliation: Laboratory of Immunology, Institute of Biological Sciences, Triângulo Mineiro Federal University, 38025-180 Uberaba, MG, Brazil.
authors.forename: Virmondes
authors.initials: V
authors.lastname: Rodrigues
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology; D009161:Mycobacterium / Q000276:immunology*; D013045:Species Specificity; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014019:Tissue Donors; D014157:Transcription Factors / Q000378:metabolism*; D014376:Tuberculosis / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology
chemical_list: D000942:Antigens, Bacterial; D016207:Cytokines; D014157:Transcription Factors