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

Abstract

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 þ 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-a 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 infection.

Combined Dendritic Cell And Anti-TIGIT Immunotherapy Potentiate Trail+ Memory NK Cells Against HIV-1 Infected Cells

“…NK cells are innate immune cells with antiviral capacities that have been shown to be essential to control HIV replication in vivo in animal models ( 32–38 ) and in spontaneous and post-treatment controllers ( 15, 39–41 ). Although some studies point to their promising therapeutic potential against HIV-1, modulation of NK cells has been less explored ( 37, 42–47 ).…”

“…Such hyperstimulation eventually leads to an exhausted state in these immune cells that is characterized by the expression of multiple inhibitory checkpoint receptors, reduced functional properties and impaired ability to eliminate infected cells (13,14). In some cases, ART does not seem to completely restore such a dysfunctional, exhausted state in immune cells and longer periods of treatment may be required to recover responsiveness in these cells (15)(16)(17)(18). Thus, new approaches are needed to develop a more effective antiviral immune response against HIV-1 and to achieve a reduction of persistent viral reservoirs and potentially, a cure.…”

“…The copyright holder for this preprint (which this version posted April 9, 2024. ; https://doi.org/10.1101/2024.04.09.587160 doi: bioRxiv preprint infected cells in vitro and in vivo, they may not be sufficient to reduce viral reservoirs to a level capable of promoting spontaneous control or remission of infection. NK cells are innate immune cells with antiviral capacities that have been shown to be essential to control HIV replication in vivo in animal models (32)(33)(34)(35)(36)(37)(38) and in spontaneous and post-treatment controllers (15,(39)(40)(41). Although some studies point to their promising therapeutic potential against HIV-1, modulation of NK cells has been less explored (37,(42)(43)(44)(45)(46)(47).…”