title: Innate immune responses and rapid control of inflammation in African green monkeys treated or not with interferon-alpha during primary SIVagm infection.
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.
authors.affiliation: Institut Pasteur, Regulation of Retroviral Infection Unit, Paris, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Jacquelin
authors.affiliation: Institut Pasteur, Regulation of Retroviral Infection Unit, Paris, France.
authors.forename: Gaël
authors.initials: G
authors.lastname: Petitjean
authors.affiliation: Institut Pasteur, Regulation of Retroviral Infection Unit, Paris, France.
authors.forename: Désirée
authors.initials: D
authors.lastname: Kunkel
authors.affiliation: Institut Pasteur, Regulation of Retroviral Infection Unit, Paris, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Liovat
authors.affiliation: Institut Pasteur, Regulation of Retroviral Infection Unit, Paris, France; Paris Diderot University, Sorbonne Paris Cité, Paris, France.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Jochems
authors.affiliation: Division of Pathology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Rogers
authors.affiliation: Institut Pasteur, Regulation of Retroviral Infection Unit, Paris, France.
authors.forename: Mickaël J
authors.initials: MJ
authors.lastname: Ploquin
authors.affiliation: Institut Pasteur, Emerging Diseases Epidemiology Unit, Paris, France.
authors.forename: Yoann
authors.initials: Y
authors.lastname: Madec
authors.affiliation: Institut Pasteur, Regulation of Retroviral Infection Unit, Paris, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Barré-Sinoussi
authors.affiliation: CEA, Division of Immuno-Virology, DSV, iMETI, Fontenay-aux-Roses, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dereuddre-Bosquet
authors.affiliation: Saint-Vincent de Paul Hospital & Paris Descartes University, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Lebon
authors.affiliation: CEA, Division of Immuno-Virology, DSV, iMETI, Fontenay-aux-Roses, France.
authors.forename: Roger
authors.initials: R
authors.lastname: Le Grand
authors.affiliation: Division of Pathology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States of America.
authors.forename: François
authors.initials: F
authors.lastname: Villinger
authors.affiliation: Institut Pasteur, Regulation of Retroviral Infection Unit, Paris, France.
authors.forename: Michaela
authors.initials: M
authors.lastname: Müller-Trutwin
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D007113:Immunity, Innate / Q000187:drug effects*; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000821:virology; D016898:Interferon-alpha / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D016898:Interferon-alpha