Isoniazid induces apoptosis of activated CD4+ T cells: implications for post-therapy tuberculosis reactivation and reinfection.

Tousif S, Singh DK, Ahmad S, Moodley P, Bhattacharyya M, Van Kaer L, Das G
J Biol Chem. 2014 289 (44): 30190-30195

PMID: 25202011 · PMCID: PMC4215201 · DOI:10.1074/jbc.C114.598946

Tuberculosis (TB) remains the second highest killer from a single infectious disease worldwide. Current therapy of TB is lengthy and consists of multiple expensive antibiotics, in a strategy referred to as Directly Observed Treatment, Short Course (DOTS). Although this therapy is effective, it has serious disadvantages. These therapeutic agents are toxic and are associated with the development of a variety of drug-resistant TB strains. Furthermore, patients treated with DOTS exhibit enhanced post-treatment susceptibility to TB reactivation and reinfection, suggesting therapy-related immune impairment. Here we show that Isoniazid (INH) treatment dramatically reduces Mycobacterium tuberculosis antigen-specific immune responses, induces apoptosis in activated CD4(+) T cells, and renders treated animals vulnerable to TB reactivation and reinfection. Consequently, our findings suggest that TB treatment is associated with immune impairment.

© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

MeSH Terms (14)

Animals Antitubercular Agents Apoptosis CD4-Positive T-Lymphocytes Cell Proliferation Cytokines Humans Immunosuppression Isoniazid Latent Tuberculosis Lymphocyte Activation Mice, Inbred BALB C Mycobacterium tuberculosis Spleen

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