CD4+ T-cell-independent mechanisms suppress reactivation of latent tuberculosis in a macaque model of HIV coinfection
| Autor: | Foreman, Taylor W, Mehra, Smriti, LoBato, Denae N, Malek, Adel, Alvarez, Xavier, Golden, Nadia A, Bucşan, Allison N, Didier, Peter J, Doyle-Meyers, Lara A, Russell-Lodrigue, Kasi E, Roy, Chad J, Blanchard, James, Kuroda, Marcelo J, Lackner, Andrew A, Chan, John, Khader, Shabaana A, Jacobs, William R, Kaushal, Deepak |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
CD4-Positive T-Lymphocytes
CD4 T cells HIV Infections CD8 T cells Lymphocyte Activation Vaccine Related Rare Diseases Latent Tuberculosis Nonhuman primate Animals Humans Tuberculosis 2.1 Biological and endogenous factors Aetiology Lung Cell Proliferation B cells Coinfection Prevention Simian immunodeficiency virus HIV Mycobacterium tuberculosis Macaca mulatta Infectious Diseases Good Health and Well Being tuberculosis HIV/AIDS Simian Immunodeficiency Virus Immunization Infection Immunologic Memory |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America, vol 113, iss 38 |
| Popis: | The synergy between Mycobacterium tuberculosis (Mtb) and HIV in coinfected patients has profoundly impacted global mortality because of tuberculosis (TB) and AIDS. HIV significantly increases rates of reactivation of latent TB infection (LTBI) to active disease, with the decline in CD4(+) T cells believed to be the major causality. In this study, nonhuman primates were coinfected with Mtb and simian immunodeficiency virus (SIV), recapitulating human coinfection. A majority of animals exhibited rapid reactivation of Mtb replication, progressing to disseminated TB and increased SIV-associated pathology. Although a severe loss of pulmonary CD4(+) T cells was observed in all coinfected macaques, a subpopulation of the animals was still able to prevent reactivation and maintain LTBI. Investigation of pulmonary immune responses and pathology in this cohort demonstrated that increased CD8(+) memory T-cell proliferation, higher granzyme B production, and expanded B-cell follicles correlated with protection from reactivation. Our findings reveal mechanisms that control SIV- and TB-associated pathology. These CD4-independent protective immune responses warrant further studies in HIV coinfected humans able to control their TB infection. Moreover, these findings will provide insight into natural immunity to Mtb and will guide development of novel vaccine strategies and immunotherapies. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|