Innate immune dysfunction and persistent activation in South African HIV elite controllers.

Area of Science:

• Immunology
• Virology
• Infectious Diseases

Background:

• Elite controllers (PWH_EC) spontaneously control HIV-1 without treatment but face non-AIDS complications.
• The innate immune response in HIV-1 control is understudied compared to adaptive immunity.
• Antigen-presenting cells (APCs) play a crucial role in innate immunity and HIV-1 pathogenesis.

Purpose of the Study:

• To evaluate the quality of innate immune responses by assessing APC phenotype and function in South African adults living with HIV.
• To compare innate immune profiles between HIV elite controllers, HIV progressors, and HIV-uninfected individuals.
• To identify potential biomarkers of immune activation and inflammation in different HIV infection groups.

Main Methods:

• Analysis of monocyte subsets, T cell and monocyte activation, and cytokine production (TNF-α, IFN-α, IL-1β) in monocytes and dendritic cells (mDCs, pDCs).
• Stimulation of cells using Toll-like receptor (TLR) ligands (LPS, CL097, CpG-ODN2216).
• Measurement of plasma biomarkers soluble CD14 (sCD14) and D-dimer using ELISA.

Main Results:

• Reduced CD86 expression on monocytes and lower frequency of classical monocytes in PWH_EC compared to HIV-uninfected controls.
• Diminished TNF-α and IL-1β production by monocytes and mDCs in PWH_EC post-stimulation.
• Elevated sCD14 levels in PWH_EC indicating persistent immune activation, and increased D-dimer in PWH_PROG suggesting higher inflammation.

Conclusions:

• PWH_EC exhibit innate immune profiles characterized by reduced monocyte activation, fewer classical monocytes, and impaired pro-inflammatory cytokine production.
• Despite viral control, PWH_EC show signs of persistent immune activation and elevated biomarkers linked to adverse outcomes.
• Findings underscore the necessity for continuous monitoring and therapeutic strategies to address chronic inflammation in PWH_EC.