Macrophages: Key Cellular Players in HIV Infection and Pathogenesis.

Area of Science:

• Immunology
• Virology
• Pathophysiology

Background:

• Macrophages and dendritic cells, myeloid lineage cells, alongside CD4+ T lymphocytes, are recognized HIV-1 targets.
• Their specific roles in HIV-1 pathophysiology were initially underestimated.
• Recent evidence highlights macrophages' significant direct and indirect involvement in HIV-1 pathogenesis.

Purpose of the Study:

• To review recent and older data on the critical functions of tissue macrophages in HIV-1 infection.
• To elucidate macrophages' roles as HIV-1 target cells and regulators of innate immunity and inflammation.

Main Methods:

• In vitro cell culture systems.
• In vivo studies using monkey and humanized mouse models.
• Analysis of data from HIV-1-infected patients.

Main Results:

• Macrophages are implicated in all stages of HIV-1 pathogenesis, including transmission, dissemination, and persistence.
• They establish viral reservoirs with latently infected CD4+ T cells, hindering HIV eradication.
• Infected macrophages, often multinucleated giant cells, are found in most tissues and persist long-term.
• Macrophages contribute to chronic inflammation and associated disorders in people living with HIV, even with antiretroviral therapy.

Conclusions:

• Tissue macrophages are crucial HIV-1 target cells found in nearly all host tissues.
• They play vital roles in viral persistence, reservoir formation, and immune regulation.
• Macrophages significantly contribute to the chronic inflammation observed in HIV-1 infection, impacting overall disease progression.