Frontiers in Cellular and Infection Microbiology (May 2022)
E3 Ligase FBXW7 Facilitates Mycobacterium Immune Evasion by Modulating TNF-α Expression
- Jingrui Song,
- Jingrui Song,
- Jingrui Song,
- Jin Chao,
- Jin Chao,
- Jin Chao,
- Xiaohong Hu,
- Xiaohong Hu,
- Xin Wen,
- Xin Wen,
- Xin Wen,
- Cairong Ding,
- Cairong Ding,
- Cairong Ding,
- Dan Li,
- Dan Li,
- Ding Zhang,
- Ding Zhang,
- Ding Zhang,
- Ding Zhang,
- Shanshan Han,
- Shanshan Han,
- Shanshan Han,
- Xiang Yu,
- Xiang Yu,
- Xiang Yu,
- Bo Yan,
- Zhu Jin,
- Zhu Jin,
- Yinhong Song,
- Yinhong Song,
- Yinhong Song,
- Jacqueline Gonzales,
- Laura E. Via,
- Laura E. Via,
- Lu Zhang,
- Decheng Wang,
- Decheng Wang,
- Decheng Wang
Affiliations
- Jingrui Song
- Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, China
- Jingrui Song
- Institute of Infection and Inflammation, China Three Gorges University, Yichang, China
- Jingrui Song
- Medical College, China Three Gorges University, Yichang, China
- Jin Chao
- Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, China
- Jin Chao
- Institute of Infection and Inflammation, China Three Gorges University, Yichang, China
- Jin Chao
- Medical College, China Three Gorges University, Yichang, China
- Xiaohong Hu
- Institute of Infection and Inflammation, China Three Gorges University, Yichang, China
- Xiaohong Hu
- Department of Tuberculosis, The Third People’s Hospital of Yichang, Yichang, China
- Xin Wen
- Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, China
- Xin Wen
- Institute of Infection and Inflammation, China Three Gorges University, Yichang, China
- Xin Wen
- Medical College, China Three Gorges University, Yichang, China
- Cairong Ding
- Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, China
- Cairong Ding
- Institute of Infection and Inflammation, China Three Gorges University, Yichang, China
- Cairong Ding
- Medical College, China Three Gorges University, Yichang, China
- Dan Li
- Institute of Infection and Inflammation, China Three Gorges University, Yichang, China
- Dan Li
- Department of Tuberculosis, The Third People’s Hospital of Yichang, Yichang, China
- Ding Zhang
- Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, China
- Ding Zhang
- Institute of Infection and Inflammation, China Three Gorges University, Yichang, China
- Ding Zhang
- Medical College, China Three Gorges University, Yichang, China
- Ding Zhang
- Department of Pathology, Yichang Central People’s Hospital, Yichang, China
- Shanshan Han
- Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, China
- Shanshan Han
- Institute of Infection and Inflammation, China Three Gorges University, Yichang, China
- Shanshan Han
- Medical College, China Three Gorges University, Yichang, China
- Xiang Yu
- Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, China
- Xiang Yu
- Institute of Infection and Inflammation, China Three Gorges University, Yichang, China
- Xiang Yu
- Medical College, China Three Gorges University, Yichang, China
- Bo Yan
- Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
- Zhu Jin
- Institute of Infection and Inflammation, China Three Gorges University, Yichang, China
- Zhu Jin
- Department of Tuberculosis, The Third People’s Hospital of Yichang, Yichang, China
- Yinhong Song
- Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, China
- Yinhong Song
- Institute of Infection and Inflammation, China Three Gorges University, Yichang, China
- Yinhong Song
- Medical College, China Three Gorges University, Yichang, China
- Jacqueline Gonzales
- Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, and Tuberculosis Imaging Program, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
- Laura E. Via
- Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, and Tuberculosis Imaging Program, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
- Laura E. Via
- Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
- Lu Zhang
- Engineering Research Center of Gene Technology, Ministry of Education, Department of Microbiology, School of Life Science, Fudan University, Shanghai, China
- Decheng Wang
- Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, China
- Decheng Wang
- Institute of Infection and Inflammation, China Three Gorges University, Yichang, China
- Decheng Wang
- Medical College, China Three Gorges University, Yichang, China
- DOI
- https://doi.org/10.3389/fcimb.2022.851197
- Journal volume & issue
-
Vol. 12
Abstract
Tumor necrosis factor alpha (TNF-α) is a crucial factor in the control of Mycobacterium tuberculosis (Mtb) infection. Pathogenic mycobacteria can inhibit and/or regulate host cell TNF-α production in a variety of ways to evade antituberculosis (anti-TB) immunity as well as facilitate immune escape. However, the mechanisms by which TNF-α expression in host cells is modulated to the benefit of mycobacteria is still an interesting topic and needs further study. Here, we report that macrophages infected with Mycobacterium marinum (Mm)—a close relative of Mtb—upregulated the expression of E3 ubiquitin ligase FBXW7. Specific silencing FBXW7 with small interfering RNA (siRNA) significantly elevates TNF-α expression and eventually promotes the elimination of intracellular bacteria. In turn, overexpression of FBXW7 in Raw264.7 macrophages markedly decreased TNF-α production. Furthermore, partial inhibition of FBXW7 in an Mm-infected murine model significantly reduced TNF-α tissue content, alleviated tissue damage as well as reduced the bacterial load of mouse tails. Finally, FBXW7 could decrease TNF-α in a K63-linked ubiquitin signaling dependent manner. Taken together, our study uncovered a previously unknown role of FBXW7 in regulating TNF-α dynamics during mycobacterial infection, which provides new insights into understanding the role of FBXW7 in anti-tuberculosis immunity and its related clinical significance.
Keywords
