Early Lesion of Post-Primary Tuberculosis: Subclinical Driver of Disease and Target for Vaccines and Host-Directed Therapies
| Autor: | Robert E. Brown, Robert L. Hunter |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Microbiology (medical)
Tuberculosis pathology_pathobiology Disease tuberculosis secretory antigens bronchiolar epithelium alveolar pneumocytes M2 polarization COX-2 FAS pathogenesis early lesion Article Lesion Pathogenesis medicine Immunology and Allergy Molecular Biology Bronchiolar epithelium Subclinical infection Primary tuberculosis General Immunology and Microbiology Host (biology) business.industry allergology medicine.disease Infectious Diseases Immunology Medicine medicine.symptom business |
| Zdroj: | Pathogens, Vol 10, Iss 1572, p 1572 (2021) Pathogens; Volume 10; Issue 12; Pages: 1572 Pathogens |
| ISSN: | 2076-0817 |
| Popis: | Research on the pathogenesis of tuberculosis in recent years has focused largely on the granulomatous stage of primary tuberculosis. However, post-primary tuberculosis that accounts for 80% of clinical disease is seldom studied because of the paucity of animal models and human tissues. The early lesion of post-primary tuberculosis is a subclinical obstructive lobular pneumonia that develops asymptomatically for months accumulating secreted mycobacterial antigens in alveolar macrophages and highly sensitized T cells before onset of clinical disease. Here we demonstrate antigen of M. tuberculosis in the cytoplasm of ciliated bronchiolar epithelium and alveolar pneumocytes in association with elements of the programmed death ligand 1 (PD-L1), cyclo-oxygenase (COX)-2, and fatty acid synthase (FAS) pathways in the early lesion. This suggests a new synthesis of the pathogenesis of post-primary tuberculosis in which M. tuberculosis use its secreted antigens and cord factor to direct prolonged subclinical development of the early lesions in preparation for a sudden necrotizing reaction sufficient to produce a cavity and/or granulomas. Available evidence indicates that most successful human and animal vaccines and host directed therapies of post-primary tuberculosis target the early lesion, not granulomas. Recognition of this will facilitate design and evaluation of improved vaccines and therapies for tuberculosis. |
| Databáze: | OpenAIRE |
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