Impaired inflammatory resolution with severe SARS-CoV-2 infection in leptin knock out obese hamster

Impaired inflammatory resolution with severe SARS-CoV-2 infection in leptin knock out obese hamster

Summary: Comorbidities, such as obesity, increase the risk of severe COVID-19. However, the mechanisms underlying severe illnesses in individuals with obesity are poorly understood. Here, we used gene-edited leptin knock out (Leptin−/−) obese hamsters to establish a severe infection model. This mode...

Full description

Saved in:
Bibliographic Details
Main Authors: Ren-Di Jiang, Yun-Zhe Luo, Hao-Feng Lin, Xiao-Shuang Zheng, Wen-Tao Zeng, Mei-Qin Liu, Hao-Hao Deng, Qi Wang, Ya-Na Lai, Ying Chen, Zi-Shuo Guo, Ya Zeng, Qian-Chun Gong, Chen Qiu, Mei Dong, Xi Wang, Zi-Yi Wang, Li-Na Ji, Pan-Pan Hou, Qian Li, Xu-Rui Shen, Bei Li, Yun Gao, Ai-Hua Zhang, Ting-Ting Jiang, Ai-Min Shi, Peng Zhou, Xin-Hua Lin, Zi-Qing Deng, Jian-Min Li, Zheng-Li Shi
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:iScience
Subjects:
Immune response
Virology
Omics
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004225000975
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Summary: Comorbidities, such as obesity, increase the risk of severe COVID-19. However, the mechanisms underlying severe illnesses in individuals with obesity are poorly understood. Here, we used gene-edited leptin knock out (Leptin−/−) obese hamsters to establish a severe infection model. This model exhibits robust viral replication, severe lung lesions, pronounced clinical symptoms, and fatal infection, mirroring severe COVID-19 in patients with obesity. Using single-cell transcriptomics on lung tissues pre- and post-infection, we found that monocyte-derived alveolar macrophages (MD-AM) play a key role in lung hyper-inflammation, including two unique MD-AM cell fate branches specific to Leptin−/− hamsters. Notably, reduced Trem2-dependent efferocytosis pathways in Leptin−/− hamsters indicated weakened inflammation resolution, consistent with the scRNA-seq data from patients with obesity. In summary, our study highlights the obesity-associated mechanisms underlying severe SARS-CoV-2 infections and establishes a reliable preclinical animal model for developing obesity-specific therapeutics for critical COVID-19.
ISSN:2589-0042

Similar Items