Related Experiment Video
Updated: Jan 9, 2026
Isolation, Transfection, and Culture of Primary Human Monocytes
Published on: December 16, 2019
Inflammatory and redox reprogramming of macrophages by HIV cell-to-cell transmission inhibits bone resorption
Franco A Sviercz1, Patricio Jarmoluk1, Constanza Russo1
1Laboratorio de Inmunopatología Viral, Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Insights
Human immunodeficiency virus (HIV) cell-to-cell spread impairs osteoclast differentiation by reprogramming macrophage precursors. This viral transmission causes inflammation and oxidative stress, blocking bone formation and offering potential therapeutic targets.
Area of Science:
- Immunology
- Cell Biology
- Bone Biology
Background:
- People with HIV often experience bone loss, a complication whose underlying mechanisms related to viral spread remain incompletely understood.
- Osteoclastogenesis, the process of bone-resorbing cell formation, is crucial for bone remodeling and is implicated in bone diseases.
Purpose of the Study:
- To investigate whether cell-to-cell transmission of HIV from infected CD4+ T cells to macrophages reprograms these precursors and impairs osteoclast differentiation.
- To elucidate the molecular mechanisms, including inflammasome activation, adhesion molecule upregulation, and reactive oxygen species (ROS) production, involved in HIV-induced osteoclastogenesis defects.
Main Methods:
- Co-culture of Jurkat cells infected with R5- or X4-tropic HIV with human monocyte-derived macrophages (M0/M1/M2).
- Quantification of HIV infection markers (p24/GFP), inflammasome activation and cell death (IL-1β, AnnexinV/7-AAD), adhesion molecules/tetraspanins (ICAM-1, LFA-1, CD9/CD63/CD81), mitochondrial ROS (mROS), and osteoclastogenesis markers (TRAP, actin ring, bone resorption).
Main Results:
- R5 HIV infection of macrophages via cell-to-cell contact sustained viral replication and significantly reduced osteoclast formation and bone resorption.
- HIV-exposed macrophages exhibited inflammasome-linked cell death and IL-1β induction, with enhanced cell-cell adhesion and upregulation of ICAM-1, LFA-1, and tetraspanins.
- HIV-infected T cells induced pro-inflammatory cytokine profiles, skewing macrophages toward an M1-like state and promoting ROS accumulation, which impaired osteoclastogenesis.
Conclusions:
- HIV cell-to-cell spread reprograms macrophage precursors, inducing inflammation and redox imbalance that critically blocks osteoclast differentiation and function.
- Targeting inflammasome activation, adhesion pathways, and ROS production presents potential therapeutic strategies to preserve bone health in individuals with HIV.
Introduction:
People with HIV experience bone loss, but how viral spread perturbs osteoclastogenesis remains unclear. We asked whether cell-to-cell transmission of HIV from infected CD4+ T cells to macrophages reprograms precursors and impairs osteoclast differentiation.
Methods:
We co-cultured Jurkat cells infected with R5- or X4-tropic HIV with human monocyte-derived macrophages (M0/M1/M2) and quantified infection (p24/GFP), inflammasome activation and death (IL-1β, AnnexinV/7-AAD, z-YVAD), adhesion molecules/tetraspanins (ICAM-1, LFA-1, CD9/CD63/CD81), mROS (MitoSOX, NAC), polarization markers/cytokines, and osteoclastogenesis (TRAP, actin ring, CD51/61, adhesion, bone resorption).
Results:
R5 HIV infected M0>M2>M1 macrophages via contact, sustaining p24 release across differentiation and reducing TRAP+ osteoclasts and resorption. HIV-exposed macrophages showed inflammasome-linked death and IL-1β induction; contact enhanced Mf-T conjugates and upregulated ICAM-1/LFA-1 and tetraspanins. HIV-infected T cells displayed pro-inflammatory TNF-α/IFN-γ profiles, skewing macrophages toward M1-like states. Jurkat-derived ROS promoted conjugates and mROS accumulation in macrophages, while NAC reduced contact and oxidative imbalance. Nevirapine partially restored osteoclastogenesis and revealed contact-associated drug insensitivity.
Discussion:
The effects scaled with the proportion of infected T cells. HIV cell-to-cell spread induces inflammatory and redox reprogramming in macrophage precursors that blocks osteoclast differentiation and function, offering testable targets (inflammasome, adhesion, ROS) to protect bone in HIV.
Related Concept Videos
01:31Osteoclasts in Bone Remodeling
01:40Bone Remodeling
01:01Regulation of Hematopoietic Stem Cells
01:28Inflammatory Response
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...