Innate immune mechanisms in HIV elite controllers

Area of Science:

• Immunology
• Virology
• Infectious Diseases

Background:

• Elite controllers (ECs) spontaneously control HIV without antiretroviral therapy (ART).
• Innate immunity plays a crucial role in HIV pathogenesis and control.
• Understanding innate mechanisms in ECs may reveal pathways for HIV remission.

Purpose of the Study:

• To synthesize evidence on innate immune mechanisms (NK cells, DCs, monocytes, cytokines) in durable HIV control by ECs.
• To identify gaps in knowledge regarding these innate pathways.
• To explore how EC-informed innate signatures can guide HIV cure interventions.

Main Methods:

• Review of recent high-dimensional and functional studies on innate immunity in ECs.
• Analysis of phenotypic and functional characteristics of NK cells, monocytes, and DCs.
• Examination of soluble factors, including cytokine milieu, in ECs.

Main Results:

• ECs exhibit specialized NK cell phenotypes (e.g., CD69+, NKG2C+CD57+) with antiviral programming.
• Monocyte homeostasis is altered, showing heterogeneous changes and potential inflammatory perturbations.
• Dendritic cells in ECs display enhanced intrinsic antiviral programs (e.g., cGAS-STING, RIG-I) and improved antigen presentation.
• ECs maintain low circulating interferon alpha (IFN-α), indicating a tightly regulated innate immune response.

Conclusions:

• Innate immunity, via specialized cell programs, contributes significantly to durable HIV suppression in ECs.
• Current understanding of these innate pathways, especially in tissues and over time, is incomplete.
• Defining essential, sufficient, and targetable innate mechanisms is critical for developing ART-free HIV remission strategies.