Macrophages form dendrite-like pseudopods to enhance bacterial ingestion
文献类型：期刊论文
| 作者 | Fan, Changyuan10,11,12; Huang, Xinyi11,12; Mei, Jie10,11,12; Shi, Xuemeng11; Zhang, Hao9; Liang, Cong9; Cui, Shuzhi11; Xing, Yifan11; Cao, Biao8; Liu, Wei7 |
| 刊名 | EMBO JOURNAL
 |
| 出版日期 | 2025-09-01 |
| 卷号 | 44期号:17页码:4772-4802 |
| 关键词 | Macrophage Dendrite-like Pseudopods Pathogen Ingestion Actin Filaments Vimentin Intermediate Filaments |
| ISSN号 | 0261-4189 |
| DOI | 10.1038/s44318-025-00515-z |
| 通讯作者 | Lin, Zhaoyu(Linzy@nju.edu.cn) ; Xu, Tao(xu_tao@gzlab.ac.cn) ; Jiu, Yaming(ymjiu@siii.cas.cn) |
| 英文摘要 | Macrophages are critical innate immune cells that exhibit remarkable adaptability during pathogen infections. However, the relationship between their morphological plasticity and physiological functions remains largely elusive. Here, we discovered an unprecedented paradigm of macrophage adaptation within a few hours upon severe Gram-negative bacterial infections, characterized by the formation of dendrite-like pseudopods (DLPs). Using in vitro, microfluidic, and in vivo infection models, we demonstrate that these pseudopods enhance bacterial uptake by expanding the macrophage searching radius, thereby bolstering host defense. Mechanistically, Toll-like receptor 4 (TLR4) activation by Gram-negative bacterial lipopolysaccharide (LPS) upregulates the expression of macrophage-specific RhoGEF and ARHGEF3 in an NF-kappa B-dependent manner. ARHGEF3 localizes to dendrite-like pseudopods and enhances RhoA activity. Consequently, periodic cycles of actin assembly and disassembly propel the elongation of pseudopods, whereas vimentin intermediate filaments stabilize them. Importantly, infusion of DLP-equipped macrophages into Salmonella-infected mice reduced bacterial burden and infection severity. Together, our findings underscore how the dynamic response of macrophages to massive infections can augment immune defense against pathogenic bacteria. |
| WOS关键词 | FOCAL ADHESIONS ; SALMONELLA ; ACTIVATION ; INHIBITION ; RHOA ; MECHANISMS ; ALIGNMENT ; DYNAMICS ; GEF-H1 ; TLR4 |
| 资助项目 | MOST | National Natural Science Foundation of China (NSFC)[32222022] ; MOST | National Natural Science Foundation of China (NSFC)[92354301] ; National Natural Science Foundation of China[23ZR1470900] ; Natural Science Foundation of Shanghai[GZNL2023A03004] ; R&D Program of Guangzhou National Laboratory[2024YFC2310003] ; R&D Program of Guangzhou National Laboratory[2022YFC2303502] ; Key Research and Development Program, Ministry of Science and Technology of China |
| WOS研究方向 | Biochemistry & Molecular Biology ; Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:001537814600001 |
| 出版者 | SPRINGERNATURE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/321147]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Lin, Zhaoyu; Xu, Tao; Jiu, Yaming |
| 作者单位 | 1.Nanjing Univ, Natl Resource Ctr Mutant Mice China,Key Lab Mode l, Nanjing Drum Tower Hosp,Jiangsu Key Lab Mol Med,Sc, Model Anim Res Ctr,State Key Lab Pharmaceut Biotec, Nanjing 210061, Peoples R China 2.Fudan Univ, Shanghai Med Coll, Canc Inst, Dept Oncol,Shanghai Canc Ctr, Shanghai 200032, Peoples R China 3.Fudan Univ, Shanghai Med Coll, Sch Basic Med Sci, Dept Biochem & Mol Biol, Shanghai 200032, Peoples R China 4.Fudan Univ, Shanghai Med Coll, MOE Key Lab Metab & Mol Med, Shanghai 200032, Peoples R China 5.Univ Macau, Fac Hlth Sci, Dept Biomed Sci, Taipa 999074, Macau, Peoples R China 6.Guangzhou Lab, Guangzhou 510005, Peoples R China 7.Fudan Univ, Shanghai Xuhui Cent Hosp, Shanghai Stomatol Hosp,Inst Biomed Sci,Dept Chem, Zhongshan Xuhui Hosp,Shanghai Key Lab Med Epigenet, Zhongshan 200032, Shanghai, Peoples R China 8.Chinese Acad Sci, Shanghai Inst Nutr & Hlth, State Key Lab Expt Hematol, Shanghai 200031, Peoples R China 9.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Ctr Excellence Mol Cell Sci, State Key Lab Cell Biol, Shanghai 200031, Peoples R China 10.Univ Chinese Acad Sci, Yuquan Rd 19 A, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Fan, Changyuan,Huang, Xinyi,Mei, Jie,et al. Macrophages form dendrite-like pseudopods to enhance bacterial ingestion[J]. EMBO JOURNAL,2025,44(17):4772-4802. |
| APA | Fan, Changyuan.,Huang, Xinyi.,Mei, Jie.,Shi, Xuemeng.,Zhang, Hao.,...&Jiu, Yaming.(2025).Macrophages form dendrite-like pseudopods to enhance bacterial ingestion.EMBO JOURNAL,44(17),4772-4802. |
| MLA | Fan, Changyuan,et al."Macrophages form dendrite-like pseudopods to enhance bacterial ingestion".EMBO JOURNAL 44.17(2025):4772-4802. |
入库方式： OAI收割
来源：上海药物研究所
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