Particle uptake driven phagocytosis in macrophages and neutrophils enhances bacterial clearance

巨噬细胞和中性粒细胞的颗粒摄取驱动吞噬作用增强了细菌清除率

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作者:Preeti Sharma, Anjali Vijaykumar, Jayashree Vijaya Raghavan, Supriya Rajendra Rananaware, Alakesh Alakesh, Janhavi Bodele, Junaid Ur Rehman, Shivani Shukla, Virta Wagde, Savitha Nadig, Sveta Chakrabarti, Sandhya S Visweswariah, Dipankar Nandi, Balasubramanian Gopal, Siddharth Jhunjhunwala

Abstract

Humans are exposed to numerous synthetic foreign particles in the form of drug delivery systems and diagnostic agents. Specialized immune cells (phagocytes) clear these particles by phagocytosing and attempting to degrade them. The process of recognition and internalization of the particles may trigger changes in the function of phagocytes. Some of these changes, especially the ability of a particle-loaded phagocyte to take up and neutralize pathogens, remains poorly studied. Herein, we demonstrate that the uptake of non-stimulatory cargo-free particles enhances the phagocytic ability of monocytes, macrophages and neutrophils. The enhancement in phagocytic ability was independent of particle properties, such as size or the base material constituting the particle. Additionally, we show that the increased phagocytosis was not a result of cellular activation or cellular heterogeneity but was driven by changes in cell membrane fluidity and cellular compliance. A consequence of the enhanced phagocytic activity was that particulate-laden immune cells neutralize Escherichia coli (E. coli) faster in culture. Moreover, when administered in mice as a prophylactic, particulates enable faster clearance of E. coli and Staphylococcus epidermidis. Together, we demonstrate that the process of uptake induces cellular changes that favor additional phagocytic events. This study provides insights into using non-stimulatory cargo-free particles to engineer immune cell functions for applications involving faster clearance of phagocytosable abiotic and biotic material.

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