Dual role of hypoxia-inducible factor 1 α in experimental pulmonary tuberculosis: its implication as a new therapeutic target

• Published in: Future microbiology 2018-06, Vol.13 (7), p.785-798
• Main Authors: Baay-Guzman, Guillermina J, Duran-Padilla, Marco A, Rangel-Santiago, Jesus, Tirado-Rodriguez, Belen, Antonio-Andres, Gabriela, Barrios-Payan, Jorge, Mata-Espinosa, Dulce, Klunder-Klunder, Miguel, Vega, Mario I, Hernandez-Pando, Rogelio, Huerta-Yepez, Sara
• Format: Article
• Language: English
• Subjects: 2-ME; 2-Methoxyestradiol - administration & dosage; Animals; Antibiotics; Antigens; Antitubercular Agents - administration & dosage; Apoptosis; Apoptosis - drug effects; Automation; Bid; Biotechnology; Chemotherapy; Combined treatment; Committees; digital pathology; Disease; Disease Models, Animal; Experiments; HIF-1α; Histopathology; Hospitals; Humans; Hypoxia; Hypoxia-inducible factor 1; Hypoxia-Inducible Factor 1, alpha Subunit - antagonists & inhibitors; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Hypoxia-inducible factors; Immunohistochemistry; Infections; Lungs; Macrophages; Macrophages - cytology; Macrophages - metabolism; Male; Medical research; Mice; Mice, Inbred BALB C; Pneumonia; Proteins; pulmonary tuberculosis; Therapeutic applications; Tuberculosis; Tuberculosis, Pulmonary - drug therapy; Tuberculosis, Pulmonary - genetics; Tuberculosis, Pulmonary - metabolism; Tuberculosis, Pulmonary - physiopathology
• ISSN: 1746-0913; 1746-0921
• DOI: 10.2217/fmb-2017-0168

Investigate the role of hypoxia-inducible factor-1α (HIF-1α) in pulmonary tuberculosis (TB). A model of progressive pulmonary TB in BALB/c mice, immunohistochemistry and digital pathology were used. High HIF-1α expression was observed during early TB in activated macrophages. During late TB, even higher HIF-1α expression was observed in foamy macrophages, which are resistant to apoptosis. Blocking HIF-1α during early infection with 2-methoxyestradiol worsened the disease, while during late TB, it induced macrophage apoptosis and decreased bacillary loads. HIF-1α has a dual role in experimental TB. This finding could have therapeutic implications because combined treatment with 2-methoxyestradiol and antibiotics appeared to eliminate mycobacteria more efficiently than conventional chemotherapy during advanced disease.