Transcriptional regulation following Mycobacterium tuberculosis infection

Master's Thesis

Abstract

Tumor necrosis factor alpha (TNF-Ìå±) and nitric oxide synthase 2 (NOS2) are crucial in the control of Mycobacterium tuberculosis infection. Previous studies have shown that murine macrophages produce lower levels of TNF-Ìå± and NOS2 following infection with pathogenic mycobacteria compared to non-pathogenic mycobacteria. Here we compare the virulent (H37Rv) and avirulent (H37Ra) isogenic strains of M. tuberculosis and their ability to activate TNF-Ìå± and NOS2 at a transcriptional level. We determined that macrophages infected with H37Rv compared to H37Ra and M. smegmatis showed diminished TNF-Ìå± and NOS2 promoter activity. Differences in the ability of the isogenic strains to activate the transcription factors Ets/Elk and NF-Ìå¼B were also observed. The reduced ability of H37Rv to activate Ets/Elk correlates with diminished TNF-Ìå± production by infected cells relative to cells infected with H37Ra. This work demonstrates that virulent M. tuberculosis is capable of modulating the host immune response at a transcriptional level.

Attributes

Attribute NameValues
URN
  • etd-12122008-103859

Author Rebecca L. Geister
Advisor Jeff Schorey
Contributor Jeff Schorey, Committee Chair
Contributor Crislyn DSouza-Schorey, Committee Member
Contributor Mary Ann McDowell, Committee Member
Degree Level Master's Thesis
Degree Discipline Biological Sciences
Degree Name MS
Defense Date
  • 2008-12-05

Submission Date 2008-12-12
Country
  • United States of America

Subject
  • NOS2

  • mycobacteria

  • TNF-α

  • cytokines

  • H37Rv

  • promoter mutants

  • luciferase

  • H37Ra

Publisher
  • University of Notre Dame

Language
  • English

Record Visibility Public
Content License
  • All rights reserved

Departments and Units

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