Freeze-thaw Microfluidic System Produces "Themis" Nanocomplex for Cleaning Persisters-infected Macrophages and Enhancing Uninfected Macrophages.

Macrophages are the primary effectors against potential pathogen infections. They can be "parasitized" by intracellular bacteria, serving as "accomplices", protecting intracellular bacteria and even switching them to persisters. Here, using a freeze-thaw strategy-based microfluidic chip, we created a "Themis" nanocomplex (TNC). The TNC consisted of Lactobacillus reuteri-derived membrane vesicles, heme, and vancomycin, which cleaned infected macrophages and enhanced uninfected macrophages. In infected macrophages, TNC released heme that led to the reconstruction of the respiratory chain complexes of intracellular persisters, forcing them to regrow. The revived bacteria produced virulence factors that destroyed host macrophages (accomplices), thereby being externalized and becoming vulnerable to immune responses. In uninfected macrophages, TNC upregulated the TCA cycle and oxidative phosphorylation (OXPHOS), contributing to immunoenhancement. The combined effect of TNC of cleaning the accomplice (infected macrophages) and reinforcing uninfected macrophages provides a promising strategy for intracellular bacterial therapy. This article is protected by copyright. All rights reserved.

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This article is protected by copyright. All rights reserved.