Mycobacterium indicus pranii (MIP) mediated host protective intracellular mechanisms against tuberculosis infection: Involvement of TLR-4 mediated signaling

• Published in: Tuberculosis (Edinburgh, Scotland) Scotland), 2016-12, Vol.101, p.201-209
• Main Author: Majumdar, Subrata
• Format: Article
• Language: English
• Subjects: Activation; Animals; Cells, Cultured; Cytokine; Cytokines - biosynthesis; Dose-Response Relationship, Immunologic; Immune response; Immune system; Immunomodulation; Infections; Infectious Disease; Inflammation; Innate immunity; Intracellular signalling; Kinases; Macrophages; Macrophages, Peritoneal - immunology; Macrophages, Peritoneal - microbiology; MAP kinase; Mice, Inbred C57BL; Microbial Sensitivity Tests - methods; Mycobacterium; Mycobacterium indicus pranii; Mycobacterium tuberculosis - immunology; NF-κB protein; Nitric Oxide - biosynthesis; Nontuberculous Mycobacteria - immunology; p38 Mitogen-Activated Protein Kinases - metabolism; Pathogens; Proteins; Pulmonary/Respiratory; Signal Transduction - immunology; Therapeutic applications; TLR-4; TLR4 protein; Toll-Like Receptor 4 - biosynthesis; Toll-Like Receptor 4 - immunology; Toll-like receptors; Tuberculosis; Tuberculosis - immunology; Up-Regulation - immunology
• ISSN: 1472-9792; 1873-281X
• DOI: 10.1016/j.tube.2016.09.027

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.