Functional Correlation between Myeloid Cells and Membrane Abundance

In the past few decades, with the rapid development of science and technology, human understanding of the immune system has continuously deepened. Among all immune cells, professional phagocytes (such as neutrophils and macrophages) play a crucial role in clearing apoptotic cells, cell debris, and invading pathogens. These cells uptake and engulf foreign substances through phagocytosis, an evolutionarily highly conserved behavior that is essential for the normal physiological functions of multicellular organisms. However, dysregulation of phagocytosis is associated with various diseases, including increased susceptibility to infections, autoimmune diseases, neurodegenerative diseases, and atherosclerosis.

Despite many achievements in the biochemical regulatory mechanisms of phagocytosis, our understanding of the biophysical and biochemical patterns of this process remains limited. This research project, published by Benjamin Y. Winer and his team in Science Immunology (Title: Plasma membrane abundance dictates phagocytic capacity and functional cross-talk in myeloid cells, Date: June 7, 2024), involves multiple research institutions, including Memorial Sloan Kettering Cancer Center and the University of California, San Francisco.

The research team found that the abundance of the plasma membrane (cell membrane) is a key regulatory factor in phagocyte behavior. By knocking out the gene for the Gβ4 protein subunit, they observed significant membrane expansion in neutrophils and macrophages, accompanied by a notable decrease in membrane tension. These biophysical changes facilitated the phagocytosis of bacteria, fungi, apoptotic cell corpses, and cancer cells. Furthermore, the researchers found that neutrophils lacking Gβ4 had impaired normal inhibition of migration ability after uptake of cellular material. In vivo, neutrophils from Gβ4 knockout mice not only showed enhanced phagocytic capacity for fungal spores inhaled into the lungs but also increased ability to transport phagocytosed pathogens to other organs. These results reveal an unexpected and important biophysical control mechanism, central to functional decision-making in myeloid cells.

Winer and his colleagues first detailed how biochemical pathways influence phagocytosis, particularly how protein molecules mediate the recognition of extracellular objects and how signaling pathways drive the wrapping of cargo. They also noted that phagocytosis is a strongly physical process and thus may be subject to dual regulation by biophysical and biochemical patterns. This was the focus of their study in this research report. By knocking out the Gβ4 subunit, the researchers discovered its important role in cell phagocytosis and migration, providing new insights and possible therapeutic methods for regulating immune cells.

Through this study, Winer and his team not only elucidated the biophysical mechanisms that occur in phagocytosis but also emphasized the potential value of these mechanisms for understanding and treating diseases associated with phagocytosis misalignment. Future research could explore manipulating immune cell activity by targeting the cellular architecture foundation, thereby regulating immune cell function without targeting specific points. This research may pave the way for new treatments for systemic microbial infections and enhance the anti-tumor potential of engineered chimeric antigen receptor (CAR) macrophages.