2. Academic Validation
  3. Macrophages form dendrite-like pseudopods to enhance bacterial ingestion

Macrophages form dendrite-like pseudopods to enhance bacterial ingestion

  • EMBO J. 2025 Sep;44(17):4772-4802. doi: 10.1038/s44318-025-00515-z.
Changyuan Fan 1 2 3,  Xinyi Huang 1 2,  Jie Mei 1 2 3,  Xuemeng Shi 2,  Hao Zhang 4,  Cong Liang 4,  Shuzhi Cui 2,  Yifan Xing 2,  Biao Cao 5,  Wei Liu 6,  Huisheng Liu 7,  Bo Liu 1 2 3,  Wakam Chang 8,  Mengle Shao 1 2 3,  Gong-Hong Wei 9,  Yan-Jun Liu 6,  Zheng-Jun Chen 4,  Zhaoyu Lin 10,  Tao Xu 11 12,  Yaming Jiu 13 14 15
Affiliations

Affiliations

  • 1 Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 201203, Shanghai, China.
  • 2 Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, 200031, Shanghai, China.
  • 3 University of Chinese Academy of Sciences, Yuquan Road No. 19(A), Shijingshan District, 100049, Beijing, China.
  • 4 State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, 200031, Shanghai, China.
  • 5 State Key Laboratory of Experimental Hematology, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, 200031, Shanghai, China.
  • 6 Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Shanghai Key Laboratory of Medical Epigenetics, Shanghai Stomatological Hospital, Institutes of Biomedical Sciences, Department of Chemistry, Fudan University, 200032, Shanghai, China.
  • 7 Guangzhou Laboratory, 510005, Guangzhou, China.
  • 8 Department of Biomedical Sciences, Faculty of Health Sciences, University of Macau, Taipa, 999074, Macau, China.
  • 9 MOE Key Laboratory of Metabolism and Molecular Medicine & Department of Biochemistry and Molecular Biology of School of Basic Medical Sciences, and Fudan University Shanghai Cancer Center, Cancer Institutes, Department of Oncology, Shanghai Medical College of Fudan University, 200032, Shanghai, China.
  • 10 State Key Laboratory of Pharmaceutical Biotechnology, Ministry of Education Key Laboratory of Model Animal for Disease Study, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, National Resource Center for Mutant Mice of China, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, 210061, Nanjing, China. [email protected].
  • 11 University of Chinese Academy of Sciences, Yuquan Road No. 19(A), Shijingshan District, 100049, Beijing, China. [email protected].
  • 12 Guangzhou Laboratory, 510005, Guangzhou, China. [email protected].
  • 13 Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 201203, Shanghai, China. [email protected].
  • 14 Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, 200031, Shanghai, China. [email protected].
  • 15 University of Chinese Academy of Sciences, Yuquan Road No. 19(A), Shijingshan District, 100049, Beijing, China. [email protected].
PMID: 40721684 DOI: 10.1038/s44318-025-00515-z
Abstract

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-κB-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.

Keywords

Actin Filaments; Dendrite-like Pseudopods; Macrophage; Pathogen Ingestion; Vimentin Intermediate Filaments.

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