HIV/SIV infection primes monocytes and dendritic cells for apoptosis.

• Main Authors: Mireille Laforge, Laure Campillo-Gimenez, Valérie Monceaux, Marie-Christine Cumont, Bruno Hurtrel, Jacques Corbeil, John Zaunders, Carole Elbim, Jérôme Estaquier
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2011-06-01
• Series: PLoS Pathogens
• Online Access: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21731488/pdf/?tool=EBI

Subversion or exacerbation of antigen-presenting cells (APC) death modulates host/pathogen equilibrium. We demonstrated during in vitro differentiation of monocyte-derived macrophages and monocyte-derived dendritic cells (DCs) that HIV sensitizes the cells to undergo apoptosis in response to TRAIL and FasL, respectively. In addition, we found that HIV-1 increased the levels of pro-apoptotic Bax and Bak molecules and decreased the levels of anti-apoptotic Mcl-1 and FLIP proteins. To assess the relevance of these observations in the context of an experimental model of HIV infection, we investigated the death of APC during pathogenic SIV-infection in rhesus macaques (RMs). We demonstrated increased apoptosis, during the acute phase, of both peripheral blood DCs and monocytes (CD14(+)) from SIV(+)RMs, associated with a dysregulation in the balance of pro- and anti-apoptotic molecules. Caspase-inhibitor and death receptors antagonists prevented apoptosis of APCs from SIV(+)RMs. Furthermore, increased levels of FasL in the sera of pathogenic SIV(+)RMs were detected, compared to non-pathogenic SIV infection of African green monkey. We suggest that inappropriate apoptosis of antigen-presenting cells may contribute to dysregulation of cellular immunity early in the process of HIV/SIV infection.