# Maintenance of intestinal CX3CR1+ macrophage homeostasis defines post-treatment control in SIV-infected macaques

## TL;DR

The study shows that preserving a specific type of intestinal macrophage in SIV-infected macaques is linked to long-term viral remission after treatment stops.

## Contribution

The study identifies CX3CR1+ intestinal macrophages as a potential biomarker for post-treatment control in SIV infection.

## Key findings

- PTC macaques maintain CX3CR1high macrophages and reduced immune activation compared to non-controllers.
- CX3CR1high macrophage abundance inversely correlates with viral burden and pro-inflammatory cytokines.
- Loss of CX3CR1high macrophages is associated with CD4+ T cell depletion and persistent viral infection.

## Abstract

Achieving durable viral remission without antiretroviral therapy (ART) remains a central challenge in HIV-1 cure research. Using a pathogenic SIV model in male cynomolgus macaques, we investigated mucosal and systemic immune features associated with post-treatment control (PTC). Chronic SIV infection disrupts intestinal macrophage homeostasis, skewing the compartment toward a CX3CR1low inflammatory phenotype marked by increased expression of costimulatory and homing markers. This polarization is associated with mucosal CD4+ T cell depletion, elevated neutrophil activation, and systemic cytokine induction. Non-controllers exhibit a similar inflammatory profile. In contrast, PTCs maintain CX3CR1high macrophages, preserve regulatory CD4 + T cells, and exhibit attenuated mucosal and systemic immune activation, resembling uninfected animals. CX3CR1high macrophage abundance inversely correlates with viral burden, T cell activation, and pro-inflammatory cytokines, suggesting a potential role in post-treatment control. These findings identify CX3CR1-expressing intestinal macrophages as a potential biomarker of mucosal immune regulation and highlight their relevance as targets in HIV cure strategies.

A better understanding of post-treatment control after therapy cessation can help design therapeutic strategies for people living with HIV. Here the authors show in a SIV macaque model that intestinal CX3CR1+ macrophages are preserved in SIV post-treatment controllers, while their loss is associated with increased CD4+ T cell activation and viral persistence, linking mucosal immune balance to long-term viral remission.