Work

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

Year: 2026

Type: article

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.

Source: Journal of Extracellular Vesicles

DOI: 10.1002/jev2.70238