Journal article
Loss of memory B cells during chronic HIV infection is driven by Foxo3a-and TRAIL-mediated apoptosis
The Journal of clinical investigation, v 121(10), pp 3877-3888
01 Oct 2011
PMID: 21926463
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Loss of memory B cells occurs from the onset of HIV-1 infection and persists into the chronic stages of infection. Lack of survival of these cells, even in subjects being treated, could primarily be the consequence of an altered local microenvironment induced by HIV infection. In this study we showed that memory B cell survival was significantly decreased in aviremic successfully treated (ST) subjects compared with subjects who control viral load as a result of natural immunity (elite controller [EC]) or with uninfected control (HIV-) subjects. The lower survival levels observed in memory B cells from ST subjects were the result of disrupted IL-2 signaling that led to increased transcriptional activity of Foxo3a and increased expression of its proapoptotic target TRAIL. Notably, memory B cell survival in ST subjects was significantly enhanced by the addition of exogenous IL-2 in a Foxo3a-dependent manner. We further showed that Foxo3a silencing by siRNA resulted in decreased expression of TRAIL and apoptosis levels in memory B cells from ST subjects. Our results thus establish a direct role for Foxo3a/TRAIL signaling in the persistence of memory B cells and provide a mechanism for the reduced survival of memory B cells during HIV infection. This knowledge could be exploited for the development of therapeutic and preventative HIV vaccines.
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Details
- Title
- Loss of memory B cells during chronic HIV infection is driven by Foxo3a-and TRAIL-mediated apoptosis
- Creators
- Julien Van Grevenynghe - Vaccine & Gene Therapy Institute of FloridaRafael A. Cubas - Université de MontréalAlessandra Noto - Université de MontréalSandrina DaFonseca - Université de MontréalZhong He - Université de MontréalYoav Peretz - Université de MontréalAbdelali Filali-Mouhim - Université de MontréalFranck P. Dupuy - Université de MontréalFrancesco A. Procopio - Université de MontréalNicolas Chomont - Université de MontréalRobert S. Balderas - BD Biosciences (United States)Elias A. Said - Czech Academy of Sciences, Institute of MicrobiologyMohamed-Rachid Boulassel - University of Health and Allied SciencesCecile L. Tremblay - Université de MontréalJean-Pierre Routy - McGill UniversityRafick-Pierre Sekaly - McGill UniversityElias K. Haddad - Vaccine & Gene Therapy Institute of Florida
- Publication Details
- The Journal of clinical investigation, v 121(10), pp 3877-3888
- Publisher
- Amer Soc Clinical Investigation Inc
- Number of pages
- 12
- Grant note
- Genome Quebec NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA DP1DA028871 / NATIONAL INSTITUTE ON DRUG ABUSE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA); European Commission CIHR; Canadian Institutes of Health Research (CIHR) Genome Canada Fonds de Recherche en Sante du Quebec (FRSQ); Fonds de la Recherche en Sante du Quebec Canadian Network for Vaccines and Immunotherapeutics P01AI076174 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine; Infectious Diseases (and HIV Medicine); Drexel University
- Web of Science ID
- WOS:000295601000017
- Scopus ID
- 2-s2.0-80053399756
- Other Identifier
- 991020099425704721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Medicine, Research & Experimental