title: HIV/SIV infection primes monocytes and dendritic cells for apoptosis.
abstract: 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.
authors: INSERM U955, Faculté Créteil Henri Mondor, Créteil, France.
authors: Mireille
authors: M
authors: Laforge
authors: Laure
authors: L
authors: Campillo-Gimenez
authors: Valérie
authors: V
authors: Monceaux
authors: Marie-Christine
authors: MC
authors: Cumont
authors: Bruno
authors: B
authors: Hurtrel
authors: Jacques
authors: J
authors: Corbeil
authors: John
authors: J
authors: Zaunders
authors: Carole
authors: C
authors: Elbim
authors: Jérôme
authors: J
authors: Estaquier
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000473:pathology; D017209:Apoptosis / Q000276:immunology*; D002522:Chlorocebus aethiops; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology*; D053222:Fas Ligand Protein; D015658:HIV Infections / Q000276:immunology / Q000473:pathology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D008253:Macaca mulatta; D009000:Monocytes / Q000276:immunology / Q000473:pathology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000473:pathology*; D053221:TNF-Related Apoptosis-Inducing Ligand
chemical_list: D053222:Fas Ligand Protein; D053221:TNF-Related Apoptosis-Inducing Ligand