Foxo3a: An integrator of immune dysfunction during HIV infection

Julien Van Grevenynghe, Rafael A. Cubas, Sandrina DaFonseca, Talibah Metcalf, Cecile L. Tremblay, Lydie Trautmann, Rafick Pierre Sekaly, John Schatzle, Elias K. Haddad

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)215-221
Number of pages7
JournalCytokine and Growth Factor Reviews
Volume23
Issue number4-5
DOIs
StatePublished - Aug 2012
Externally publishedYes

Keywords

  • Apoptosis
  • EC
  • Foxo3a
  • HIV
  • Memory
  • Microenvironment

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Immunology and Allergy
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

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