Effective innate immune response in natural HIV-1 controllers. Can mimicking lead to novel preventive and cure strategies against HIV-1?

Purpose of reviewHIV-1 controller individuals represents a model that can be useful for the development of novel vaccines and therapies. Initial studies pointed to the involvement of improved adaptive immunity, however, new emerging evidence suggests the contribution of innate cells to effective antiviral responses in spontaneous controllers. Therefore, understanding the alterations on innate cell subsets might be crucial to develop new effective therapeutic strategies.Recent findingsAmong different innate immune cells, dendritic cell (DC) and natural killer (NK) cell are essential for effective antiviral responses. DC from controllers display improved innate detection of HIV-1 transcripts, higher induction of interferons, higher antigen presenting capacities and increased metabolism and higher capacities to induce polyfunctional CD8+T-cell responses. Such properties have been mimicked by Toll-like receptor ligands and applied to DC-based immunotherapies in humans and in animal models. NK cells from controllers display higher expression of activating receptors promoting increased antibody-dependent cellular cytotoxicity (ADCC) and natural cytotoxicity activities. Neutralizing antibodies in combination with interleukin-15 superagonist or interferon-α can increase ADCC and cytotoxicity in NK cells from HIV-1 progressors.SummaryMimicking DC and NK cell innate profiles in controllers has become a promising strategy to step forward a novel efficient immunotherapy against the HIV-1 infectionE.M.G. was supported by the Ramo´n y Cajal Program (RYC2018-024374-I), the MINECO/FEDER RETOS program (RTI2018-097485-A-I00), Comunidad de Madrid Talento Program (2017-T1/BMD-5396), Gilead becas de investigacio´n (GLD19/00168), by Centro de Investigacio´n Biome´dica en Red (CIBERINF) de Enfermedades Infecciosas (CB21/13/00107), La Caixa Banking Foundation (H20-00218) and by REDINCOV grant from Fundacio´ La Marato´ TV3. M.C.M. was supported by La Caixa Banking Foundation (H20-00218) and Gilead becas de investigacio´n (GLD19/00168