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  3. Extracellular Vesicles Coordinate Bacterial Cloaking in Lung Epithelial Cells to Alleviate Acute Inflammatory Injury

Extracellular Vesicles Coordinate Bacterial Cloaking in Lung Epithelial Cells to Alleviate Acute Inflammatory Injury

  • J Extracell Vesicles. 2026 Feb;15(2):e70238. doi: 10.1002/jev2.70238.
Feng Ding 1 2 3,  Shengkai Gong 1 3,  Haotian Luo 1 3,  Dandan Wu 2,  Xiaoshan Yang 1 3,  Zihan Li 1,  Dingmei Zhang 1 4,  Peijie He 5,  Jiani Liu 6,  Lili Bao 1 3,  Yang Zhou 1 3,  Zhengyan Wang 1 3,  Siying Liu 7,  Pei Wang 2,  Geng Dou 1,  Shiyu Liu 1
Affiliations

Affiliations

  • 1 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Oral Biology & Clinic of Oral Rare Diseases and Genetic Disease, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, China.
  • 2 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Radiology, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, China.
  • 3 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, China.
  • 4 Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.
  • 5 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, China.
  • 6 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Digital Center, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, China.
  • 7 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, China.
PMID: 41656978 DOI: 10.1002/jev2.70238
Abstract

The capacity of host professional phagocytes to attenuate excessive inflammatory responses through pathogen cloaking during Infection has been well-established. However, the involvement of non-professional phagocytes in this process remains unknown. Here, we identify a previously unrecognized mechanism by which lung epithelial cells (LECs) attenuate inflammatory responses during Staphylococcus aureus Infection. S. aureus-challenged LECs rapidly shed extracellular vesicles (EVs) carrying surface receptors capable of binding invading bacteria and forming EV-bacteria complexes. The EV-bacteria complexes were internalized by LECs via RhoA-ROCK1-actin-driven endocytosis pathway, reducing free Bacterial burden within the alveolar lumen. This EV-mediated pathogen cloaking conferred acute-phase protection, as demonstrated by mitigating early-stage pulmonary inflammation, and improving survival rates in infected mice. Paradoxically, this strategy permitted chronic Bacterial persistence and sustaining low-grade inflammation. Our findings delineate a trade-off mechanism that non-professional phagocytes modulate acute Bacterial infection and inflammatory responses via pathogen cloaking. This mechanistic perspective reframes non-professional phagocytes as active architects of Infection outcomes based on EV-mediated host-pathogen interactions. Our work provides insights into the mechanism of Bacterial cloaking during Infection and suggests stage-specific therapeutic strategies.

Keywords

EV‐bacteria complexes; Staphylococcus aureus; acute bacterial infection; extracellular vesicles; pathogen cloaking.

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