High Turnover of Tissue Macrophages Contributes to Tuberculosis Reactivation in Simian Immunodeficiency Virus-Infected Rhesus Macaques
| Autor: | Mariluz Arainga, Chie Sugimoto, Smriti Mehra, Deepak Kaushal, Marcelo J. Kuroda, Chad J. Roy, Elizabeth S. Didier, Cecily C. Midkiff, Kristen M. Merino, Xavier Alvarez, Yanhui Cai |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes Male Simian Acquired Immunodeficiency Syndrome HIV Infections medicine.disease_cause Medical and Health Sciences Monocytes 0302 clinical medicine Immunology and Allergy Medicine Macrophage 2.1 Biological and endogenous factors 2.2 Factors relating to the physical environment Aetiology Lung Immunodeficiency Coinfection Simian immunodeficiency virus Viral Load Biological Sciences medicine.anatomical_structure Infectious Diseases HIV/AIDS Simian Immunodeficiency Virus Infection Tuberculosis Alveolar Microbiology Virus Lymphocyte Depletion Major Articles and Brief Reports 03 medical and health sciences Immune system Rare Diseases Latent Tuberculosis Macrophages Alveolar Animals business.industry Animal Monocyte Macrophages Mycobacterium tuberculosis medicine.disease Virology Macaca mulatta Disease Models Animal 030104 developmental biology Good Health and Well Being Disease Models business 030215 immunology |
| Zdroj: | The Journal of infectious diseases, vol 217, iss 12 |
| Popis: | BACKGROUND: Tuberculosis (TB) and human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) profoundly affect the immune system and synergistically accelerate disease progression. It is believed that CD4(+) T-cell depletion by HIV is the major cause of immunodeficiency and reactivation of latent TB. Previous studies demonstrated that blood monocyte turnover concurrent with tissue macrophage death from virus infection better predicted AIDS onset than CD4(+) T-cell depletion in macaques infected with simian immunodeficiency virus (SIV). METHODS: In this study, we describe the contribution of macrophages to the pathogenesis of Mycobacterium tuberculosis (Mtb)/SIV coinfection in a rhesus macaque model using in vivo BrdU labeling, immunostaining, flow cytometry, and confocal microscopy. RESULTS: We found that increased monocyte and macrophage turnover and levels of SIV-infected lung macrophages correlated with TB reactivation. All Mtb/SIV-coinfected monkeys exhibited declines in CD4(+) T cells regardless of reactivation or latency outcomes, negating lower CD4(+) T-cell levels as a primary cause of Mtb reactivation. CONCLUSIONS: Results suggest that SIV-related damage to macrophages contributes to Mtb reactivation during coinfection. This also supports strategies to target lung macrophages for the treatment of TB. |
| Databáze: | OpenAIRE |
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