title: Isoniazid induces apoptosis of activated CD4+ T cells: implications for post-therapy tuberculosis reactivation and reinfection.
abstract: 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.
authors.affiliation: School of Laboratory Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban 4001, South Africa.
authors.forename: Sultan
authors.initials: S
authors.lastname: Tousif
authors.affiliation: International Centre for Genetic Engineering and Biotechnology (ICGEB), ArunaAsaf Ali Marg, New Delhi 110067, India.
authors.forename: Dhiraj Kumar
authors.initials: DK
authors.lastname: Singh
authors.affiliation: Special Center for Molecular Medicine (SCMM), Jawaharlal Nehru University, ArunaAsaf Ali Marg, New Delhi 110067, India.
authors.forename: Shaheer
authors.initials: S
authors.lastname: Ahmad
authors.affiliation: School of Laboratory Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban 4001, South Africa.
authors.forename: Prashini
authors.initials: P
authors.lastname: Moodley
authors.affiliation: Department of Biochemistry, University of Calcutta, 35, Ballygunge Circular Road, Kolkata 700 019, India, and.
authors.forename: Maitree
authors.initials: M
authors.lastname: Bhattacharyya
authors.affiliation: Department of Pathology, Microbiology and Immunology, School of Medicine, Vanderbilt University, Nashville, Tennessee 37232.
authors.forename: Luc
authors.initials: L
authors.lastname: Van Kaer
authors.affiliation: School of Laboratory Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban 4001, South Africa,; Special Center for Molecular Medicine (SCMM), Jawaharlal Nehru University, ArunaAsaf Ali Marg, New Delhi 110067, India,. Electronic address: gobardhan.das07@gmail.com.
authors.forename: Gobardhan
authors.initials: G
authors.lastname: Das
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D007165:Immunosuppression Therapy; D007538:Isoniazid / Q000494:pharmacology*; D055985:Latent Tuberculosis / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D008213:Lymphocyte Activation / Q000187:drug effects; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000276:immunology; D013154:Spleen / Q000187:drug effects / Q000276:immunology
chemical_list: D000995:Antitubercular Agents; D016207:Cytokines; D007538:Isoniazid
keywords: Bacterial Pathogenesis; Cytokine; Immunology; Interleukin; T Helper Cells