journal article·2024-10Open access

TMEM16F Expressed in Kupffer Cells Regulates Liver Inflammation and Metabolism to Protect Against Listeria Monocytogenes

Jianlong Tang, Hua Song, Shimin Li, Sin Man Lam, Jieming Ping, Mengyun Yang, Na Li, Teding Chang, Ze Yu, Weixiang Liu, Yan Lu, Min Zhu, Zhaohui Tang, Zheng Liu, Yusong R. Guo, Guanghou Shui, André Veillette, Zhutian Zeng, Ning Wu

Advanced Science· Volume 11· Issue 39

Abstract

Abstract Infection by bacteria leads to tissue damage and inflammation, which need to be tightly controlled by host mechanisms to avoid deleterious consequences. It is previously reported that TMEM16F, a calcium‐activated lipid scramblase expressed in various immune cell types including T cells and neutrophils, is critical for the control of infection by bacterium Listeria monocytogenes (Lm) in vivo. This function correlated with the capacity of TMEM16F to repair the plasma membrane (PM) damage induced in T cells in vitro, by the Lm toxin listeriolysin O (LLO). However, whether the protective effect of TMEM16F on Lm infection in vivo is mediated by an impact in T cells, or in other cell types, is not determined. Herein, the immune cell types and mechanisms implicated in the protective effect of TMEM16F against Lm in vivo are elucidated. Cellular protective effects of TMEM16F correlated with its capacity of lipid scrambling and augment PM fluidity. Using cell type‐specific TMEM16F‐deficient mice, the indication is obtained that TMEM16F expressed in liver Kupffer cells (KCs), but not in T cells or B cells, is key for protection against Listeria in vivo. In the absence of TMEM16F, Listeria induced PM rupture and fragmentation of KCs in vivo. KC death associated with greater liver damage, inflammatory changes, and dysregulated liver metabolism. Overall, the results uncovered that TMEM16F expressed in Kupffer cells is crucial to protect the host against Listeria infection. This influence is associated with the capacity of Kupffer cell‐expressed TMEM16F to prevent excessive inflammation and abnormal liver metabolism.
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Research context

OpenAlex topics: Vibrio bacteria research studies · Immune Response and Inflammation · Escherichia coli research studies

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Immunology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology (HUST) Wuhan 430030 China

The First Affiliated Hospital of Anhui Medical University and Institute of Clinical Immunology Anhui Medical University Hefei 230032 China

The CAS Key Laboratory of Innate Immunity and Chronic Disease School of Basic Medical Sciences Division of Life Sciences and Medicine University of Science and Technology of China Hefei 230001 China

State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental Biology Chinese Academy of Sciences Beijing 100101 China

University of Chinese Academy of Sciences Beijing 100101 China

Department of biochemistry and molecular biology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China

Department of Traumatic Surgery Tongji Trauma Center Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China

Department of Otolaryngology‐Head and Neck Surgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology No. 1095 Jiefang Avenue Wuhan 430030 China

Department of Clinical Immunology The Third Affiliated Hospital of Sun Yat‐sen University Guangzhou 510630 China

Department of Thoracic Surgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China

Cell Architecture Research Center Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China

Laboratory of Molecular Oncology Institut de recherches cliniques de Montréal (IRCM) Montréal Québec H2W1R7 Canada

Department of Medicine University of Montréal Montréal Québec H3T 1J4 Canada

Department of Medicine McGill University Montréal Québec H3G 1Y6 Canada

Department of Oncology The First Affiliated Hospital of USTC University of Science and Technology of China Hefei 230001 China

Funding

National Key Research and Development Program of China · National Natural Science Foundation of China

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