Natural killer cells migrate into and control simian immunodeficiency virus replication in lymph node follicles in African green monkeys

Nicolas Huot (1, 2) , Béatrice Jacquelin (1) , Thalía Garcia-Tellez (1) , Philippe Rascle (1, 2, 3) , Mickaël Ploquin (1) , Yoann Madec (4) , R Keith Keith Reeves (5, 6) , Nathalie Derreudre-Bosquet (7, 8) , Michaela Müller-Trutwin (1, 2)

1 HIV, Inflammation et persistance - HIV, Inflammation and Persistence
2 VRI - Vaccine Research Institute
3 UPD7 - Université Paris Diderot - Paris 7
4 Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology
5 BIDMC - Beth Israel Deaconess Medical Center [Boston]
6 HMS - Harvard Medical School [Boston]
7 IMVA - U1184 - Immunologie des Maladies Virales et Autoimmunes
8 JACOB - Institut de Biologie François JACOB

Natural killer (NK) cells play an essential role in antiviral immunity, but knowledge of their function in secondary lymphoid organs is incomplete. Lymph node follicles constitute a major viral reservoir during infections with HIV-1 and simian immunodeficiency virus of macaques (SIVmac). In contrast, during nonpathogenic infection with SIV from African green monkeys (SIVagm), follicles remain generally virus free. We show that NK cells in secondary lymphoid organs from chronically SIVagm-infected African green monkeys (AGMs) were frequently CXCR5+ and entered and persisted in lymph node follicles throughout the follow-up (240 d post-infection). These follicles were strongly positive for IL-15, which was primarily presented in its membrane-bound form by follicular dendritic cells. NK cell depletion through treatment with anti-IL-15 monoclonal antibody during chronic SIVagm infection resulted in high viral replication rates in follicles and the T cell zone and increased viral DNA in lymph nodes. Our data suggest that, in nonpathogenic SIV infection, NK cells migrate into follicles and play a major role in viral reservoir control in lymph nodes.

Domains: Life Sciences [q-bio]; Immunology; Innate immunity; Human health and pathology; Infectious diseases; Microbiology and Parasitology; Virology

Nicolas Huot, Béatrice Jacquelin, Thalía Garcia-Tellez, Philippe Rascle, Mickaël Ploquin, et al.. Natural killer cells migrate into and control simian immunodeficiency virus replication in lymph node follicles in African green monkeys. Nature Medicine, 2017, 23 (11), pp.1277-1286. ⟨10.1038/nm.4421⟩. ⟨pasteur-01984650⟩