The role of transforming growth factor beta-1 in the progression of HIV/AIDS and development of non-AIDS-defining fibrotic disorders
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Frontiers Research Foundation
Abstract
Even after attainment of sustained viral suppression following implementation of highly active antiretroviral therapy, HIV-infected persons continue to experience persistent, low-grade, systemic inflammation. Among other mechanisms, this appears to result from ongoing microbial translocation from a damaged gastrointestinal tract. This HIV-related chronic inflammatory response is paralleled by counteracting, but only partially effective, biological anti-inflammatory processes. Paradoxically, however, this anti-inflammatory
response not only exacerbates immunosuppression but also predisposes
for development of non-AIDS-related, non-communicable disorders. With respect to the pathogenesis of both sustained immunosuppression and the increased frequency of non-AIDS-related disorders, the anti-inflammatory/profibrotic cytokine, transforming growth factor-β1 (TGF-β1), which remains persistently elevated in both untreated and virally suppressed HIV-infected persons, may provide a common link. In this context, the current review is focused on two different, albeit related, harmful activities of TGF-β1 in HIV infection. First, on the spectrum of anti-inflammatory/immunosuppressive activities of TGF-β1 and the involvement of this cytokine, derived predominantly from T regulatory cells, in driving disease progression in HIV-infected persons via both non-fibrotic and profibrotic mechanisms. Second, the possible involvement of sustained elevations in
circulating and tissue TGF-β1 in the pathogenesis of non-AIDS-defining cardiovascular, hepatic, pulmonary and renal disorders, together with a brief comment on potential TGF-β1-targeted therapeutic strategies.
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Highly active antiretroviral therapy, Immunosuppression, Lymphoid fibrosis, Macrophages, Non-AIDSdefining defining disorders, Non-AIDS defining disorders, Organ fibrosis, T Regulatory cells, Antiretroviral therapy (ART), Myocardial infarction, Microbial translocation, Transforming growth factor-β1 (TGF-β1), Obstructive pulmonary disease, Hepatitis-C virus, Chronic kidney disease, HIV infected patients, Human immunodeficiency virus (HIV), Regulatory T-cells
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Citation
Theron, A.J., Anderson, R., Rossouw, T.M. and Steel, H.C. (2017) The Role of Transforming Growth Factor Beta-1 in the Progression of HIV/AIDS and Development of Non-AIDS-Defining Fibrotic Disorders. Front. Immunol. 8:1461.
DOI: 10.3389/fimmu.2017.01461.