HIV/SIV Infection Primes Monocytes and Dendritic Cells for Apoptosis

PLoS Pathogens

Mireille Laforge¹  Laure Campillo-Gimenez¹  Carole Elbim¹  John Zaunders²  Marie-Christine Cumont³  Valérie Monceaux³  Bruno Hurtrel³  Jacques Corbeil⁴  Jérôme Estaquier⁵ 

[1] INSERM U955, Faculté Créteil Henri Mondor, Créteil, France;St Vincent's Centre for Applied Medical Research, St Vincent's Hospital, Darlinghurst, Australia;Unité de Physiopathologie des Infections Lentivirales, Institut Pasteur, Paris, France;Université Laval, Centre de Recherche en Infectiologie, Québec, Canada;Université Paris Descartes, UMR S 872, Paris, France

关键词: Apoptosis;    Monocytes;    Antigen-presenting cells;    Macrophages;    Cell differentiation;    HIV-1;    T cells;    Flow cytometry;   

DOI  :  10.1371/journal.ppat.1002087

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY