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

• Type of Material: Article
• Authors: Beatrice Jacquelin, Institut Pasteur; Gael Petitjean, Institut Pasteur; Desiree Kunkel, Institut Pasteur; Anne-Sophie Liovat, Institut Pasteur; Simon P. Jochems, Institut Pasteur; Kenneth A. Rogers, Emory University; Mickael J. Ploquin, Institut Pasteur; Yoann Madec, Institut Pasteur; Francoise Barre-Sinoussi, Institut Pasteur; Nathalie Dereuddre-Bosquet, Commissariat à l'Energie Atomique et aux Energies Alternatives; Pierre Lebon, St Vincent de Paul Hospital; Roger Le Grand, Commissariat à l'Energie Atomique et aux Energies Alternatives; Francois Villinger, Emory University; Michaela Mueller-Trutwin, Institut Pasteur
• Language: English
• Date: 2014-07-01
• Publisher: PUBLIC LIBRARY SCIENCE
• Publication Version: Final Published Version
• Copyright Statement: © 2014 Jacquelin et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.ppat.1004241
• Title of Journal or Parent Work: PLOS PATHOGENS
• Volume: 10
• Issue: 7
• Start Page: e1004241
• End Page: e1004241
• Grant/Funding Information: This work was supported by the French National Agency for Research on AIDS and Viral Hepatitis (ANRS), “Fondation AREVA”, Sidaction and “Fondation TOTAL”.
• Keywords: Life Sciences & Biomedicine; Parasitology; DISEASE PROGRESSION; TYPE-1 INFECTION; SIMIAN IMMUNODEFICIENCY VIRUS; CD4(+) T-CELLS; Microbiology; RHESUS MACAQUES; LYMPHOID-TISSUE; Science & Technology; Virology; SOOTY MANGABEYS; HIV-1 INFECTION; INDEPENDENT ACTIVATION; PLASMACYTOID DENDRITIC CELLS
• Research Categories: Biology, Microbiology; Biology, Parasitology; Biology, Virology

Abstract

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.