Maintenance of intestinal CX3CR1+ macrophage homeostasis defines post-treatment control in SIV-infected macaques
- Stéphane Hua
- Keltouma Benmeziane
- Delphine Desjardins
- Nastasia Dimant
- Marco Leonec
- Laetitia Bossevot
- Julien Lemaitre
- Adeline Melard
- Francis Relouzat
- Véronique Avettand-Fenoel
- Nathalie Dereuddre-Bosquet
- Asier Saez- Cirion
- Roger Le Grand
- Mariangela Cavarelli
2026-02-24
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 CX3CR1 low 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 CX3CR1 high macrophages, preserve regulatory CD4 + T cells, and exhibit attenuated mucosal and systemic immune activation, resembling uninfected animals. CX3CR1 high 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.