Innate Immune Responses and Rapid Control of Inflammation in African Green Monkeys Treated or Not with Interferon-Alpha during Primary SIVagm Infection

PLoS Pathogens

François Villinger¹  Pierre Lebon¹  Michaela Müller-Trutwin²  Mickaël J. Ploquin²  Françoise Barré-Sinoussi³  Yoann Madec⁴  Nathalie Dereuddre-Bosquet⁴  Béatrice Jacquelin⁴  Anne-Sophie Liovat⁴  Simon P. Jochems⁴  Désirée Kunkel⁴  Gaël Petitjean⁴  Kenneth A. Rogers⁵  Roger Le Grand⁶ 

[1] CEA, Division of Immuno-Virology, DSV, iMETI, Fontenay-aux-Roses, France;Division of Pathology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States of America;Institut Pasteur, Emerging Diseases Epidemiology Unit, Paris, France;Institut Pasteur, Regulation of Retroviral Infection Unit, Paris, France;Paris Diderot University, Sorbonne Paris Cité, Paris, France;Saint-Vincent de Paul Hospital & Paris Descartes University, Paris, France

关键词: NK cells;    Cytokines;    Macaque;    T cells;    Blood;    Inflammation;    Blood plasma;    Immune activation;   

DOI  :  10.1371/journal.ppat.1004241

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Chronic immune activation (IA) is considered as the driving force of CD4+ T cell depletion and AIDS. Fundamental clues in the mechanisms that regulate IA could lie in natural hosts of SIV, such as African green monkeys (AGMs). Here we investigated the role of innate immune cells and IFN-α in the control of IA in AGMs. AGMs displayed significant NK cell activation upon SIVagm infection, which was correlated with the levels of IFN-α. Moreover, we detected cytotoxic NK cells in lymph nodes during the early acute phase of SIVagm infection. Both plasmacytoid and myeloid dendritic cell (pDC and mDC) homing receptors were increased, but the maturation of mDCs, in particular of CD16+ mDCs, was more important than that of pDCs. Monitoring of 15 cytokines showed that those, which are known to be increased early in HIV-1/SIVmac pathogenic infections, such as IL-15, IFN-α, MCP-1 and CXCL10/IP-10, were significantly increased in AGMs as well. In contrast, cytokines generally induced in the later stage of acute pathogenic infection, such as IL-6, IL-18 and TNF-α, were less or not increased, suggesting an early control of IA. We then treated AGMs daily with high doses of IFN-α from day 9 to 24 post-infection. No impact was observed on the activation or maturation profiles of mDCs, pDCs and NK cells. There was also no major difference in T cell activation or interferon-stimulated gene (ISG) expression profiles and no sign of disease progression. Thus, even after administration of high levels of IFN-α during acute infection, AGMs were still able to control IA, showing that IA control is independent of IFN-α levels. This suggests that the sustained ISG expression and IA in HIV/SIVmac infections involves non-IFN-α products.

【 授权许可】

CC BY