HIV-1-Infected Human Macrophages, by Secreting RANK-L, Contribute to Enhanced Osteoclast Recruitment

• Main Authors: Rémi Mascarau, Florent Bertrand, Arnaud Labrousse, Isabelle Gennero, Renaud Poincloux, Isabelle Maridonneau-Parini, Brigitte Raynaud-Messina, Christel Vérollet
• Format: Article
• Language: English
• Published: MDPI AG 2020-04-01
• Series: International Journal of Molecular Sciences
• Subjects: HIV-1; macrophages; osteoclasts; bone defects; RANK-L; cell migration
• Online Access: https://www.mdpi.com/1422-0067/21/9/3154
• ISSN: 1661-6596; 1422-0067

HIV-1 infection is frequently associated with low bone density, which can progress to osteoporosis leading to a high risk of fractures. Only a few mechanisms have been proposed to explain the enhanced osteolysis in the context of HIV-1 infection. As macrophages are involved in bone homeostasis and are critical host cells for HIV-1, we asked whether HIV-1-infected macrophages could participate in bone degradation. Upon infection, human macrophages acquired some osteoclast features: they became multinucleated, upregulated the osteoclast markers RhoE and β3 integrin, and organized their podosomes as ring superstructures resembling osteoclast sealing zones. However, HIV-1-infected macrophages were not fully differentiated in osteoclasts as they did not upregulate NFATc-1 transcription factor and were unable to degrade bone. Investigating whether infected macrophages participate indirectly to virus-induced osteolysis, we showed that they produce RANK-L, the key osteoclastogenic cytokine. RANK-L secreted by HIV-1-infected macrophages was not sufficient to stimulate multinucleation, but promoted the protease-dependent migration of osteoclast precursors. In conclusion, we propose that, by stimulating RANK-L secretion, HIV-1-infected macrophages contribute to create a microenvironment that favors the recruitment of osteoclasts, participating in bone disorders observed in HIV-1 infected patients.