title: Mycobacterium indicus pranii (MIP) mediated host protective intracellular mechanisms against tuberculosis infection: Involvement of TLR-4 mediated signaling.
abstract: Mycobacterium tuberculosis infection inflicts the disease Tuberculosis (TB), which is fatal if left untreated. During M. tuberculosis infection, the pathogen modulates TLR-4 receptor down-stream signaling, indicating the possible involvement of TLR-4 in the regulation of the host immune response. Mycobacterium indicus pranii (MIP) possesses immuno-modulatory properties which induces the pro-inflammatory responses via induction of TLR-4-mediated signaling. Here, we observed the immunomodulatory properties of MIP against tuberculosis infection. We have studied the detailed signaling mechanisms employed by MIP in order to restore the host immune response against the in vitro tuberculosis infection. We observed that in infected macrophages MIP treatment significantly increased the TLR-4 expression as well as activation of its downstream signaling, facilitating the activation of P38 MAP kinase. MIP treatment was able to activate NF-κB via involvement of TLR-4 signaling leading to the enhanced pro-inflammatory cytokine and NO generation in the infected macrophages and generation of protective immune response. Therefore, we may suggest that, TLR4 may represent a novel therapeutic target for the activation of the innate immune response during Tuberculosis infection.
authors.affiliation: Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII- M, Kolkata, 700 054, India.
authors.forename: Shibali
authors.initials: S
authors.lastname: Das
authors.affiliation: Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII- M, Kolkata, 700 054, India.
authors.forename: Bidisha Paul
authors.initials: BP
authors.lastname: Chowdhury
authors.affiliation: Dept. of Microbiology, Institute of Post Graduate Medical Education & Research, Kolkata, India.
authors.forename: Avranil
authors.initials: A
authors.lastname: Goswami
authors.affiliation: Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII- M, Kolkata, 700 054, India.
authors.forename: Shabina
authors.initials: S
authors.lastname: Parveen
authors.affiliation: Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII- M, Kolkata, 700 054, India.
authors.forename: Junaid
authors.initials: J
authors.lastname: Jawed
authors.affiliation: Dept. of Microbiology, N.R.S Medical College, Kolkata, India.
authors.forename: Nishith
authors.initials: N
authors.lastname: Pal
authors.affiliation: Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII- M, Kolkata, 700 054, India. Electronic address: subrata@bic.boseinst.ernet.
authors.forename: Subrata
authors.initials: S
authors.lastname: Majumdar
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004306:Dose-Response Relationship, Immunologic; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000382:microbiology*; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests / Q000379:methods; D009169:Mycobacterium tuberculosis / Q000276:immunology; D009569:Nitric Oxide / Q000096:biosynthesis; D009170:Nontuberculous Mycobacteria / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D009569:Nitric Oxide; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Cytokine; MAP kinase; Mycobacterium indicus pranii; TLR-4; Tuberculosis