Isoniazid (INH) treatment of INH-resistant Mycobacterium tuberculosis inhibits infected macrophage to produce TNF-alpha.

Macrophages undergo apoptosis after infected by Mycobacterium tuber- culosis (M.tb), which is regulated by tumor necrosis factor alpha (TNF-alpha) and has a direct correlation with killing of intracellular bacilli. In order to clarify the role of isoniazid (INH) in the modulation of macrophages apoptosis and intracellular bacilli replication, we performed the following studies using an INH-resistant clinical M.tb isolate (INHres). Macrophages derived from peripheral blood were infected with INHres and treated or not treated with INH. Apoptosis was measured using an Ag-capture ELISA for histone and fragmented DNA. Production of TNF-alpha by INHres infected was assayed using ELISA and viability of intracellular M.tb was determined using bacterial culture of macrophage lysates on Lowenstein-Jensen (LJ) medium. INH pre-treatment to INHres reduced macrophages apoptosis, production of TNF-alpha and intracellular INHres viability. This study indicated that INH affected TNF-alpha release resulting in reduction of the extent macrophages apoptosis and of intracellular INH-resistant M.tb viability.

[1]  T. Wibawa,et al.  Apoptosis and Phagocytosis Activity of Macrophages Infected by Mycobacterium tuberculosis Resistant and Sensitive Isoniazid Clinical Isolates , 2015 .

[2]  M. Arcila,et al.  Activation of apoptosis, but not necrosis, during Mycobacterium tuberculosis infection correlated with decreased bacterial growth: role of TNF-alpha, IL-10, caspases and phospholipase A2. , 2007, Cellular immunology.

[3]  Xueqiong Wu,et al.  Comparison of Three Methods for Rapid Identification of Mycobacterial Clinical Isolates to the Species Level , 2007, Journal of Clinical Microbiology.

[4]  S. Pizzo,et al.  LMP-420, a small-molecule inhibitor of TNF-alpha, reduces replication of HIV-1 and Mycobacterium tuberculosis in human cells , 2006, AIDS research and therapy.

[5]  J. Gómez-Reino,et al.  Effectiveness of recommendations to prevent reactivation of latent tuberculosis infection in patients treated with tumor necrosis factor antagonists. , 2005, Arthritis and rheumatism.

[6]  D. Brooks,et al.  The Glycan-Rich Outer Layer of the Cell Wall of Mycobacterium tuberculosis Acts as an Antiphagocytic Capsule Limiting the Association of the Bacterium with Macrophages , 2004, Infection and Immunity.

[7]  R. Appelberg,et al.  Induction of Mycobacterium avium growth restriction and inhibition of phagosome-endosome interactions during macrophage activation and apoptosis induction by picolinic acid plus IFNgamma. , 2004, Microbiology.

[8]  Toshiko Yamamoto,et al.  Effect of Mycobacterium bovis BCG Vaccinationon Mycobacterium-Specific Cellular Proliferation and TumorNecrosis Factor Alpha Production from Distinct Guinea PigLeukocytePopulations , 2003, Infection and Immunity.

[9]  L. Bermudez,et al.  Mycobacterium tuberculosis infection causes different levels of apoptosis and necrosis in human macrophages and alveolar epithelial cells , 2003, Cellular microbiology.

[10]  M. Rojas,et al.  Modulation of macrophage apoptosis by antimycobacterial therapy: physiological role of apoptosis in the control of Mycobacterium tuberculosis. , 2003, Toxicology and applied pharmacology.

[11]  M. Röllinghoff,et al.  Induction of TNF in Human Alveolar Macrophages As a Potential Evasion Mechanism of Virulent Mycobacterium tuberculosis1 , 2002, The Journal of Immunology.

[12]  J. Keane,et al.  Differential Effects of a Toll-Like Receptor Antagonist on Mycobacterium tuberculosis-Induced Macrophage Responses1 , 2001, The Journal of Immunology.

[13]  C. E. Barry,et al.  The genetics and biochemistry of isoniazid resistance in mycobacterium tuberculosis. , 2000, Microbes and infection.

[14]  C. Montesano,et al.  Mycobacterium tuberculosis-induced apoptosis in monocytes/macrophages: early membrane modifications and intracellular mycobacterial viability. , 2000, The Journal of infectious diseases.

[15]  Hardy Kornfeld,et al.  Virulent Mycobacterium tuberculosis Strains Evade Apoptosis of Infected Alveolar Macrophages1 , 2000, The Journal of Immunology.

[16]  H. Nikaido,et al.  A mutant of Mycobacterium smegmatis defective in the biosynthesis of mycolic acids accumulates meromycolates. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[17]  H. Macdonald,et al.  Fas ligand-induced apoptosis of infected human macrophages reduces the viability of intracellular Mycobacterium tuberculosis. , 1998, Journal of immunology.

[18]  W. Rom,et al.  Copyright © 1997, American Society for Microbiology Effects of Mycobacteria on Regulation of Apoptosis in , 1997 .

[19]  M. Piacentini,et al.  APOPTOSIS OF HUMAN MONOCYTES/MACROPHAGES IN MYCOBACTERIUM TUBERCULOSIS INFECTION , 1997, The Journal of pathology.

[20]  J. Keane,et al.  Infection by Mycobacterium tuberculosis promotes human alveolar macrophage apoptosis , 1997, Infection and immunity.

[21]  R. Urbanczik,et al.  Isoniazid protects mice against endotoxin lethality without influencing tumor necrosis factor synthesis and release , 1991, Antimicrobial Agents and Chemotherapy.

[22]  K. Takayama,et al.  Effect ofIsoniazid on theIn VivoMycolic Acid Synthesis, CellGrowth, andViability of Mycobacterium tuberculosis , 1972 .