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Tuberculosis (TB) is a contagious infection primarily affecting the lung parenchyma but which can also affect other body parts. TB can be classified based on disease development, presentation, and the affected anatomical site.
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Tuberculosis, or TB, is a bacterial infectious disease caused by Mycobacterium tuberculosis. While its primary impact is on the lungs, leading to pulmonary tuberculosis, it can also affect various other organs, a condition referred to as extrapulmonary tuberculosis.
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LAG3 expression in active Mycobacterium tuberculosis infections.

Bonnie L Phillips1, Smriti Mehra2, Muhammad H Ahsan3

  • 1Division of Bacteriology, Tulane National Primate Research Center, Covington, Louisiana; Biomedical Sciences Graduate Student Program, New Orleans, Louisiana; National Institute of Respiratory Diseases, Mexico City, Mexico.

The American Journal of Pathology
|January 1, 2015
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Lymphocyte-activation gene 3 (LAG3) expression increases in the lungs during active tuberculosis infection in macaques. This immune marker is not elevated during latent infection but reactivates with co-infection, indicating its role in active disease.

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Area of Science:

  • Immunology
  • Microbiology
  • Pathogen-host interactions

Background:

  • Mycobacterium tuberculosis (MTB) establishes persistent lung infections by modulating host immunity.
  • Lymphocyte-activation gene 3 (LAG3) is an immunomodulatory protein expressed on T cells.
  • Understanding immune responses during MTB infection is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the role and expression patterns of LAG3 during Mycobacterium tuberculosis infection in a nonhuman primate model.
  • To determine if LAG3 expression correlates with active versus latent tuberculosis.
  • To explore the impact of co-infections on LAG3 expression in the context of tuberculosis.

Main Methods:

  • Utilized a rhesus macaque model of tuberculosis, mimicking human infection.
  • Analyzed LAG3 expression in lung tissues and granulomatous lesions.
  • Compared LAG3 expression in experimentally infected macaques with latent tuberculosis and those with active disease or co-infections.

Main Results:

  • LAG3 expression was significantly induced in the lungs and granulomas of macaques with active MTB infection.
  • LAG3 was not induced in animals with latent tuberculosis infection.
  • Simian immunodeficiency virus co-infection reactivated latent tuberculosis, leading to increased LAG3 expression in the lungs.
  • LAG3 was primarily found on CD4(+) T cells and natural killer cells, correlating with high bacterial loads and altered T-cell responses.

Conclusions:

  • LAG3 expression serves as a marker for active Mycobacterium tuberculosis infection in the lungs.
  • The induction of LAG3 is specific to active tuberculosis and its reactivation, not seen in latent infection or other pathogen challenges.
  • LAG3 expression patterns provide insights into immune dynamics during tuberculosis and co-infections.