tetano
Editor, Senior Moderator
iScience
. 2025 Feb 26;28(3):112116.
doi: 10.1016/j.isci.2025.112116. eCollection 2025 Mar 21. Dual role of HO-1 in mediating antiviral immune responses and mitigating excessive inflammatory damage during influenza virus infection
Linlin Ma[SUP] 1 [/SUP], Peng Zhang[SUP] 2 3 4 [/SUP], Xingqiong Li[SUP] 2 3 4 [/SUP], Baihe Sun[SUP] 1 [/SUP], Yuhuan Li[SUP] 2 3 4 [/SUP], Jiandong Jiang[SUP] 2 3 4 [/SUP]
Affiliations
Influenza A virus (IAV) remains a global health threat, with severe cases causing high morbidity and mortality. Type I interferons (IFN-α/β) are crucial for early innate immunity to IAV but can drive immunopathology. This study investigates the role of heme oxygenase-1 (HO-1), a stress-responsive protein with anti-inflammatory properties, in modulating the immune response to IAV. Lung-tropic adeno-associated virus (AAV)-mediated HO-1 overexpression reduces lung damage by limiting immune cells infiltration, including plasmacytoid dendritic cells and classical monocytes, while promoting regulatory T cells (Tregs) and nonclassical monocytes. Additionally, HO-1 increases macrophage populations, enhancing antiviral responses via IFN pathways. Consistent with this, HO-1 knockout mice experience more severe infections, and HO-1 recruit inhibited IAV replication and alleviated pulmonary inflammation. In addition, compared with wide-type, the catalytically inactive mutation (H25A) impairs HO-1's anti-inflammatory function. These findings underscore HO-1's critical role in balancing antiviral immunity and inflammation, positioning it as a potential therapeutic target for severe influenza.
Keywords: biochemistry; immunology; virology.
. 2025 Feb 26;28(3):112116.
doi: 10.1016/j.isci.2025.112116. eCollection 2025 Mar 21. Dual role of HO-1 in mediating antiviral immune responses and mitigating excessive inflammatory damage during influenza virus infection
Linlin Ma[SUP] 1 [/SUP], Peng Zhang[SUP] 2 3 4 [/SUP], Xingqiong Li[SUP] 2 3 4 [/SUP], Baihe Sun[SUP] 1 [/SUP], Yuhuan Li[SUP] 2 3 4 [/SUP], Jiandong Jiang[SUP] 2 3 4 [/SUP]
Affiliations
- PMID: 40160414
- PMCID: PMC11951048
- DOI: 10.1016/j.isci.2025.112116
Influenza A virus (IAV) remains a global health threat, with severe cases causing high morbidity and mortality. Type I interferons (IFN-α/β) are crucial for early innate immunity to IAV but can drive immunopathology. This study investigates the role of heme oxygenase-1 (HO-1), a stress-responsive protein with anti-inflammatory properties, in modulating the immune response to IAV. Lung-tropic adeno-associated virus (AAV)-mediated HO-1 overexpression reduces lung damage by limiting immune cells infiltration, including plasmacytoid dendritic cells and classical monocytes, while promoting regulatory T cells (Tregs) and nonclassical monocytes. Additionally, HO-1 increases macrophage populations, enhancing antiviral responses via IFN pathways. Consistent with this, HO-1 knockout mice experience more severe infections, and HO-1 recruit inhibited IAV replication and alleviated pulmonary inflammation. In addition, compared with wide-type, the catalytically inactive mutation (H25A) impairs HO-1's anti-inflammatory function. These findings underscore HO-1's critical role in balancing antiviral immunity and inflammation, positioning it as a potential therapeutic target for severe influenza.
Keywords: biochemistry; immunology; virology.