HIV/SIV infection primes monocytes and dendritic cells for apoptosis

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. © 2011 estaquier et al.