Citations 2
Temporal single-cell analysis reveals age-associated delay in immune resolution after respiratory viral infection
Wu, Yue , Li, Chaofan , Tang, Jinyi, Cheon, In Su , Zhu, Bibo, Zhang, Ruixuan, Hu, Shengen Shawn, Johnson, Aaron J, Zong, Hui, dong, Haidong, Gao, Xiaochen , Fain, Cori E. , Narasimhan, Harish , Santos, Gislane de Almeida , Ayasoufi, Katayoun , Johnson, Aaron J. , Zong, Hui , Zang, Chongzhi , Dong, Haidong , Sun, Jie
No container title available | March 12, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Aging is a major risk factor for increased morbidity and mortality following acute respiratory virus infections. To elucidate the immune determinants underlying viral pathogenesis and delayed lung repair in the aged lung, a comprehensive time-course study was conducted. Single-cell RNA sequencing (scRNAseq) and high-dimensional flow cytometry were utilized to compare lungs from young and aged mice infected with influenza A virus (IAV). Aged hosts displayed diminished alveolar macrophage (AM) and dendritic cell (DC) but elevated monocyte-derived macrophage (MoM) and interstitial macrophage (IM) presence following infection. Additionally, enhanced accumulation of adaptive immune cells, including CD4+ tissue-resident helper (TRH) cells, CD8+ tissue-resident memory (TRM) cells, and a B cell subset resembling age-associated B cells, was observed in the memory phase. Pathway analysis revealed that elevated type I and II interferon (IFNα/γ) signaling, especially in MoM/IM subsets, distinguished the aged hosts from the young. Inhibition of IFNα/γ signaling after viral clearance improved long-term respiratory outcomes and reduced both IM and TRH populations in aged mice. These findings highlight the pivotal role of IFNα/γ signaling, likely within MoM/IM subsets, in driving the exuberant persistence of adaptive immune cells and chronic immunopathology in the aged lung following acute viral infection.
Temporal single-cell analysis reveals age-associated delay in immune resolution after respiratory viral infection
Wu, Yue , Li, Chaofan , Tang, Jinyi, Cheon, In Su , Zhu, Bibo, Zhang, Ruixuan, Hu, Shengen Shawn, Johnson, Aaron J, Zong, Hui, dong, Haidong, Gao, Xiaochen , Fain, Cori E. , Narasimhan, Harish , Santos, Gislane de Almeida , Ayasoufi, Katayoun , Johnson, Aaron J. , Zong, Hui , Zang, Chongzhi , Dong, Haidong , Sun, Jie
No container title available | March 12, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Aging is a major risk factor for increased morbidity and mortality following acute respiratory virus infections. To elucidate the immune determinants underlying viral pathogenesis and delayed lung repair in the aged lung, a comprehensive time-course study was conducted. Single-cell RNA sequencing (scRNAseq) and high-dimensional flow cytometry were utilized to compare lungs from young and aged mice infected with influenza A virus (IAV). Aged hosts displayed diminished alveolar macrophage (AM) and dendritic cell (DC) but elevated monocyte-derived macrophage (MoM) and interstitial macrophage (IM) presence following infection. Additionally, enhanced accumulation of adaptive immune cells, including CD4+ tissue-resident helper (TRH) cells, CD8+ tissue-resident memory (TRM) cells, and a B cell subset resembling age-associated B cells, was observed in the memory phase. Pathway analysis revealed that elevated type I and II interferon (IFNα/γ) signaling, especially in MoM/IM subsets, distinguished the aged hosts from the young. Inhibition of IFNα/γ signaling after viral clearance improved long-term respiratory outcomes and reduced both IM and TRH populations in aged mice. These findings highlight the pivotal role of IFNα/γ signaling, likely within MoM/IM subsets, in driving the exuberant persistence of adaptive immune cells and chronic immunopathology in the aged lung following acute viral infection.