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J Biol Chem. 2014 Oct 31;289(44):30190-5. doi: 10.1074/jbc.C114.598946. Epub 2014 Sep 8.

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

Author information

1
the School of Laboratory Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban 4001, South Africa.
2
the International Centre for Genetic Engineering and Biotechnology (ICGEB), ArunaAsaf Ali Marg, New Delhi 110067, India.
3
From the Special Center for Molecular Medicine (SCMM), Jawaharlal Nehru University, ArunaAsaf Ali Marg, New Delhi 110067, India.
4
the Department of Biochemistry, University of Calcutta, 35, Ballygunge Circular Road, Kolkata 700 019, India, and.
5
the Department of Pathology, Microbiology and Immunology, School of Medicine, Vanderbilt University, Nashville, Tennessee 37232.
6
the School of Laboratory Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban 4001, South Africa, From the Special Center for Molecular Medicine (SCMM), Jawaharlal Nehru University, ArunaAsaf Ali Marg, New Delhi 110067, India, gobardhan.das07@gmail.com.

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.

KEYWORDS:

Bacterial Pathogenesis; Cytokine; Immunology; Interleukin; T Helper Cells

PMID:
25202011
PMCID:
PMC4215201
DOI:
10.1074/jbc.C114.598946
[Indexed for MEDLINE]
Free PMC Article

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