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Journal article
Foxo3a: An integrator of immune dysfunction during HIV infection
Cytokine & growth factor reviews, v 23(04-05), pp 215-221
Aug 2012
PMID: 22748238
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Chronic HIV infection, which is primarily characterized by the progressive depletion of total CD4+ T cells, also causes persistent inflammation and immune activation. This is followed by profound changes in cellular and tissue microenvironments that often lead to prolonged immune dysfunction. The global nature of this immune dysfunction suggests that factors that are involved in immune cell survival, proliferation, differentiation and maturation are all affected. Of particular interest is the transcriptional factor Foxo3a that regulates a number of genes that are critical in the development and the maintenance of T and B cells, dendritic cells (DCs) and macrophages. Alterations in the microenvironment mediated by HIV infection cause significant increase in the transcriptional activity of Foxo3a; this has major impact on T cell and B cell immunity. In fact, recent findings from HIV infected individuals highlight three important points: (1) the alteration of Foxo3a signaling during HIV infection deregulates innate and adaptive immune responses; (2) Foxo3a-mediated effects are reversible and could be restored by interfering with the Foxo3a pathway; and (3) down-regulation of Foxo3a transcriptional activity in elite controllers (ECs) represents a molecular signature, or a correlate of immunity, associated with natural protection and lack of disease progression. In this review, we will discuss how HIV-infection altered microenvironments could result in impaired immune responses via the Foxo3a signaling pathway. Defining precisely the molecular mechanisms of how persistent inflammation and immune activation are able to influence the Foxo3a pathway could ultimately help in the development of novel approaches to improve immune responses in HIV infected subjects.
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Details
- Title
- Foxo3a: An integrator of immune dysfunction during HIV infection
- Creators
- Julien van Grevenynghe - Vaccine & Gene Therapy Institute of FloridaRafael A. Cubas - Vaccine & Gene Therapy Institute of FloridaSandrina DaFonseca - Université de MontréalTalibah Metcalf - Vaccine & Gene Therapy Institute of FloridaCecile L. Tremblay - Université de MontréalLydie Trautmann - Vaccine & Gene Therapy Institute of FloridaRafick-Pierre Sekaly - Vaccine & Gene Therapy Institute of FloridaJohn Schatzle - Vaccine & Gene Therapy Institute of FloridaElias K. Haddad - ITER
- Publication Details
- Cytokine & growth factor reviews, v 23(04-05), pp 215-221
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine; Infectious Diseases (and HIV Medicine); Drexel University
- Web of Science ID
- WOS:000308844300009
- Scopus ID
- 2-s2.0-84864920849
- Other Identifier
- 991020100214804721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology