Particle uptake driven phagocytosis in macrophages and neutrophils enhances bacterial clearance

• Published in: Journal of controlled release 2022-03, Vol.343, p.131-141
• Main Authors: Sharma, Preeti, Vijaykumar, Anjali, Raghavan, Jayashree Vijaya, Rananaware, Supriya Rajendra, Alakesh, Alakesh, Bodele, Janhavi, Rehman, Junaid Ur, Shukla, Shivani, Wagde, Virta, Nadig, Savitha, Chakrabarti, Sveta, Visweswariah, Sandhya S., Nandi, Dipankar, Gopal, Balasubramanian, Jhunjhunwala, Siddharth
• Format: Article
• Language: English
• Subjects: Animals; Escherichia coli; Immuno-modulation; Macrophages - metabolism; Mice; Microparticle; Monocyte; Monocytes; Nanoparticle; Neutrophils; Phagocyte; Phagocytes; Phagocytosis
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2022.01.030

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. [Display omitted] •Uptake of particulate matter drives sequential phagocytosis in macrophages, monocytes, and neutrophils.•Increased sequential phagocytosis is not a result of Toll-like receptor driven activation or cellular heterogeneity.•Sequential phagocytosis is likely driven by changes to the fluidity of the cell membrane and cellular compliance.•One application of the enhanced phagocytosis driven by particulates is to increase the clearance rates of bacteria.