title: Immunomodulation in host-protective immune response against murine tuberculosis through regulation of the T regulatory cell function.
abstract: Tuberculosis, caused by the bacteria Mycobacterium tuberculosis, is characterized by an infection in lung and spleen. In the present study, we have elucidated the mechanism by which Mycobacterium indicus pranii renders protection in in vivo Mycobacterium tuberculosis infection. We observed that Mycobacterium indicus pranii treated infected C57BL/6 mice showed a strong host-protective Th1 immune response along with a marked decrease in immunosuppressive cytokines, TGF-β, and IL-10-secreting CD4(+) T cells. This Mycobacterium indicus pranii mediated decrease in immunosuppressive cytokines was correlated with the reduction in the elevated frequency of CD4(+)CD25(+) T regulatory cells, along with the reduced TGF-β production from these T regulatory cells in tuberculosis-infected mice. This reduction in the T regulatory cell population was a result of effective modulation of STAT4-STAT5 transcription factor counter-regulation by Mycobacterium indicus pranii, which in turn, reduced the immunosuppressive activity of T regulatory cells. Thus, these findings put forward a detailed mechanistic insight into Mycobacterium indicus pranii mediated regulation of the T regulatory cell functioning during experimental murine tuberculosis, which might be helpful in combating Mycobacterium-induced pathogenesis.
authors.affiliation: *Division of Molecular Medicine, Bose Institute, Kolkata, India; Department of Microbiology, Institute of Post Graduate Medical Education and Research, Kolkata, India; and Department of Microbiology, Nil Ratan Sircar Medical College, Kolkata, India.
authors.forename: Shibali
authors.initials: S
authors.lastname: Das
authors.affiliation: *Division of Molecular Medicine, Bose Institute, Kolkata, India; Department of Microbiology, Institute of Post Graduate Medical Education and Research, Kolkata, India; and Department of Microbiology, Nil Ratan Sircar Medical College, Kolkata, India.
authors.forename: Kuntal
authors.initials: K
authors.lastname: Halder
authors.affiliation: *Division of Molecular Medicine, Bose Institute, Kolkata, India; Department of Microbiology, Institute of Post Graduate Medical Education and Research, Kolkata, India; and Department of Microbiology, Nil Ratan Sircar Medical College, Kolkata, India.
authors.forename: Avranil
authors.initials: A
authors.lastname: Goswami
authors.affiliation: *Division of Molecular Medicine, Bose Institute, Kolkata, India; Department of Microbiology, Institute of Post Graduate Medical Education and Research, Kolkata, India; and Department of Microbiology, Nil Ratan Sircar Medical College, Kolkata, India.
authors.forename: Bidisha Paul
authors.initials: BP
authors.lastname: Chowdhury
authors.affiliation: *Division of Molecular Medicine, Bose Institute, Kolkata, India; Department of Microbiology, Institute of Post Graduate Medical Education and Research, Kolkata, India; and Department of Microbiology, Nil Ratan Sircar Medical College, Kolkata, India.
authors.forename: Nishith K
authors.initials: NK
authors.lastname: Pal
authors.affiliation: *Division of Molecular Medicine, Bose Institute, Kolkata, India; Department of Microbiology, Institute of Post Graduate Medical Education and Research, Kolkata, India; and Department of Microbiology, Nil Ratan Sircar Medical College, Kolkata, India subrata@jcbose.ac.in.
authors.forename: Subrata
authors.initials: S
authors.lastname: Majumdar
mesh_terms: D000818:Animals; D005260:Female; D016753:Interleukin-10 / Q000276:immunology*; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D050797:STAT4 Transcription Factor / Q000276:immunology; D050799:STAT5 Transcription Factor / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology* / Q000473:pathology
chemical_list: C556062:IL10 protein, mouse; D050797:STAT4 Transcription Factor; D050799:STAT5 Transcription Factor; C494091:Stat4 protein, mouse; D016212:Transforming Growth Factor beta; D016753:Interleukin-10
keywords: CD4+; FOXP3; MIP; STAT4