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

Béatrice Jacquelin (1) , Gaël Petitjean (1) , Désirée Kunkel (1) , Anne-Sophie Liovat (1) , Simon P Jochems (1, 2) , Kenneth A Rogers (3) , Mickaël Ploquin (1) , Yoann Madec (4) , François Barré-Sinoussi (1) , Nathalie Dereuddre-Bosquet (5) , Pierre Lebon (6, 2) , Roger Le Grand (5) , François Villinger (3) , Michaela Müller-Trutwin (1)

1 Régulation des Infections Rétrovirales
2 UPD7 - Université Paris Diderot - Paris 7
3 Yerkes National Primate Research Center [Lawrenceville, GA]
4 Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology
5 IMETI - Institut des Maladies Emergentes et des Thérapies Innovantes
6 Hôpital Saint-Vincent de Paul

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-a in the control of IA in AGMs. AGMs displayed significant NK cell activation upon SIVagm infection, which was correlated with the levels of IFN-a. 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-a, 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-a, were less or not increased, suggesting an early control of IA. We then treated AGMs daily with high doses of IFN-a 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-a during acute infection, AGMs were still able to control IA, showing that IA control is independent of IFN-a levels. This suggests that the sustained ISG expression and IA in HIV/SIVmac infections involves non-IFN-a products.

Domaines: Sciences du Vivant [q-bio]; Maladies infectieuses; Virologie; Immunologie; Immunité innée; Immunothérapie

Béatrice Jacquelin, Gaël Petitjean, Désirée Kunkel, Anne-Sophie Liovat, Simon P Jochems, et al.. Innate Immune Responses and Rapid Control of Inflammation in African Green Monkeys Treated or Not with Interferon-Alpha during Primary SIVagm Infection. PLoS Pathogens, 2014, 10 (7), pp.e1004241. ⟨10.1371/journal.ppat.1004241⟩. ⟨pasteur-01960800⟩