Do phagocytic receptor levels and signalling limit phagocytic capacity, appetite, and recovery ?

Candidate: Sierra Soffiaturo
Supervisor: Dr. Roberto Botelho      

ABSTRACT

Within the immune system, specialized cells, such as macrophages, play distinct roles in combating infections through processes like phagocytosis. Phagocytosis involves the recognition, uptake, and degradation of particles by phagocytes, with macrophages continuing this process until they reach their capacity. Our study aimed to investigate the mechanisms behind how macrophages reach fullness and cease uptake. We hypothesized that a depletion of Fcγ receptor (FcγR) levels would diminish the appetite of cells at phagocytic capacity. Additionally, the involvement of inhibitory signals, like ITIM-based FcγRIIb, was expected to reduce the phagocytic appetite of macrophages at capacity. Testing this hypothesis involved examining CD16 surface and total receptor levels, revealing that FcγRIII (CD16) levels remain consistent as macrophages reach phagocytic capacity. This finding indicates that CD16 levels do not limit phagocytic capacity. Furthermore, downstream effectors of both activation and inhibitory Fcγ receptor-mediated pathways were shown to be active during various stages of uptake, highlighting the role of signaling events as cells approach fullness. Our study suggests that signaling events may initiate feedback loops instructing phagocytes to halt phagocytic uptake, leading to the attainment of fullness.