Moving lipids to help cells kill microbes
Phagocytosis, i.e. the engulfment of large particles by a cell, plays a key role in immune responses. Immune cells use this process to destroy invaders that would otherwise make us sick. To form invaginations of the cell membrane able to engulf pathogens, i.e. phagocytic cups, cells need to rearrange both their cytoskeleton and the lipid composition of their membrane.
Two new players controlling phagocytosis
In a recent study published in the Journal of Cell Science and carried out as part of the PhD thesis of Dr. Mayis Kaba, researchers from the laboratory of Prof. Nicolas Demaurex and from the laboratory of Prof. Paula Nunes-Hasler demonstrated for the first time the role of two lipid transfer proteins, Nir2 and Nir3, in the process of phagocytosis. The researchers found that Nir2 and Nir3 are recruited near phagocytic cups to create an appropriate lipid composition. These changes in lipid composition act as cellular signals and lead to changes in the architecture of the cytoskeleton that promote the sealing of phagocytic cups.
By using gene editing techniques, the scientists confirmed that a lack of Nir2 and Nir3 led to modifications in the lipid composition of the cell membrane. Cells lacking Nir2 and Nir3 repeatedly attempted to engulf particles without success (see movie below), highlighting the critical role of these proteins in facilitating successful phagocytosis.
A normal cell (left movie) forms a unique actin ring to successfully engulf particles, whereas a cell lacking Nir2 and Nir3 (right movie) repeatedly attempts to form actin rings without being able to engulf particles. © Supplementary movies related to Figure 5 in Kaba et al. 2023.
Deciphering the role of Nir proteins during phagocytosis transform the understanding of this key process. These significant findings hold potential implications for fields such as immunology and cell biology, offering insights into immune disorders, infectious diseases, and other conditions related to impaired phagocytosis.
31 Jul 2023