Mechanisms of reactivation of latent tuberculosis infection due to SIV coinfection
| Autor: | Allison N. Bucsan, Deepak Kaushal, Dhiraj Kumar Singh, Mushtaq Ahmed, Breanna Threeton, Jyothi Rengarajan, Taylor W. Foreman, Ayan Chatterjee, Nadia A. Golden, James A. Hoxie, Shabaana A. Khader, Tae-Hyung Lee, Xavier Alvarez, Smriti Mehra, Melanie G. Kirkpatrick |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes Tuberculosis T cell Simian Acquired Immunodeficiency Syndrome medicine.disease_cause Lymphocyte Depletion 03 medical and health sciences 0302 clinical medicine Latent Tuberculosis medicine Animals Homeostasis biology Latent tuberculosis Effector business.industry Coinfection Concise Communication Lentivirus General Medicine Mycobacterium tuberculosis Simian immunodeficiency virus medicine.disease bacterial infections and mycoses Virology Macaca mulatta 030104 developmental biology medicine.anatomical_structure Phenotype Infectious disease (medical specialty) 030220 oncology & carcinogenesis Mutation biology.protein Simian Immunodeficiency Virus Antibody business |
| Popis: | HIV is a major driver of tuberculosis (TB) reactivation. Depletion of CD4(+) T cells is assumed to be the basis behind TB reactivation in individuals with latent tuberculosis infection (LTBI) coinfected with HIV. Nonhuman primates (NHPs) coinfected with a mutant simian immunodeficiency virus (SIVΔGY) that does not cause depletion of tissue CD4(+) T cells during infection failed to reactivate TB. To investigate the contribution of CD4(+) T cell depletion relative to other mechanisms of SIV-induced reactivation of LTBI, we used CD4R1 antibody to deplete CD4(+) T cells in animals with LTBI without lentiviral infection. The mere depletion of CD4(+) T cells during LTBI was insufficient in generating reactivation of LTBI. Instead, direct cytopathic effects of SIV resulting in chronic immune activation, along with the altered effector T cell phenotypes and dysregulated T cell homeostasis, were likely mediators of reactivation of LTBI. These results revealed important implications for TB control in HIV-coinfected individuals. |
| Databáze: | OpenAIRE |
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