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Updated: Dec 12, 2025
Isolation, Transfection, and Culture of Primary Human Monocytes
Published on: December 16, 2019
HIV Impairs Alveolar Macrophage Function via MicroRNA-144-Induced Suppression of Nrf2
Xian Fan1, Shannon C Murray1, Bashar S Staitieh1
1Division of Pulmonary, Allergy, Critical Care & Sleep Medicine, Emory University School of Medicine, Atlanta, Georgia.
Background:
Despite anti-retroviral therapy, HIV-1 infection increases the risk of pneumonia and causes oxidative stress and defective alveolar macrophage (AM) immune function. We have previously determined that HIV-1 proteins inhibit antioxidant defenses and impair AM phagocytosis by suppressing nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Given its known effects on Nrf2, we hypothesize miR-144 mediates the HIV-1 induced suppression of Nrf2.
Methods:
Primary AMs isolated from HIV-1 transgenic (HIV-1 Tg) rats and wild type littermates (WT) as well as human monocyte-derived macrophages (MDMs) infected ex vivo with HIV-1 were used. We modulated miR-144 expression using a miR-144 mimic or an inhibitor to assay its effects on Nrf2/ARE activity and AM functions in vitro and in vivo.
Results:
MiR-144 expression was increased in AMs from HIV-1 Tg rats and in HIV-1-infected human MDMs compared to cells from WT rats and non-infected human MDMs, respectively. Increasing miR-144 with a miR-144 mimic inhibited the expression of Nrf2 and its downstream effectors in WT rat macrophages and consequently impaired their bacterial phagocytic capacity and H2O2 scavenging ability. These effects on Nrf2 expression and AM function were reversed by antagonizing miR-144 ex vivo or in the airways of HIV-1 Tg rats in vivo, but this protection was abrogated by silencing Nrf2 expression.
Conclusions:
Our results suggest that inhibiting miR-144 or interfering with its deleterious effects on Nrf2 attenuates HIV-1-mediated AM immune dysfunction and improves lung health in individuals with HIV.
Insights
In HIV-1 infection, miR-144 impairs alveolar macrophage function by suppressing Nrf2. Inhibiting miR-144 restores macrophage defenses and improves lung health in HIV patients.
Area of Science:
- Immunology
- Molecular Biology
- Virology
Background:
- HIV-1 infection compromises alveolar macrophage (AM) immune function, leading to oxidative stress and increased pneumonia risk, even with anti-retroviral therapy.
- HIV-1 proteins are known to suppress antioxidant defenses and phagocytosis by inhibiting nuclear factor (erythroid-derived 2)-like 2 (Nrf2).
Purpose of the Study:
- To investigate the role of miR-144 in mediating HIV-1-induced suppression of Nrf2 in alveolar macrophages.
- To determine if modulating miR-144 can restore AM function and improve lung health in the context of HIV-1 infection.
Main Methods:
- Primary AMs from HIV-1 transgenic rats and ex vivo HIV-1-infected human monocyte-derived macrophages (MDMs) were utilized.
- miR-144 expression was modulated using mimics and inhibitors to assess effects on Nrf2/ARE activity and AM functions in vitro and in vivo.
Main Results:
- miR-144 levels were elevated in AMs from HIV-1 transgenic rats and HIV-1-infected human MDMs.
- Upregulating miR-144 impaired Nrf2 expression, bacterial phagocytosis, and hydrogen peroxide scavenging in macrophages.
- Antagonizing miR-144 reversed these deficits, but this protective effect was dependent on Nrf2 expression.
Conclusions:
- miR-144 plays a critical role in HIV-1-mediated suppression of Nrf2 and subsequent alveolar macrophage immune dysfunction.
- Inhibiting miR-144 offers a potential therapeutic strategy to restore AM function and enhance lung health in individuals with HIV.
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