Isoniazid Induces Apoptosis of Activated CD4+ T Cells: Implications for Post-therapy Tuberculosis Reactivation and Reinfection

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2014 Sep 10

PMID 25202011

Citations 31

Authors

Sultan Tousif

Dhiraj Kumar Singh

Shaheer Ahmad

Prashini Moodley

Maitree Bhattacharyya

Luc Van Kaer

Gobardhan Das

Affiliations

Soon will be listed here.

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.

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