The Molecular Basis of Phagocytosis

Phagocytosis of bacteria is one of the most important processes in the immune system, where specialized human immune cells capture, internalize, and kill bacteria. Despite many years of research, the exact molecular relationship between opsonins on the bacterial surface and phagocytic receptor activity on the human phagocyte is not known, and the importance of local environment has just started to emerge. For example, correct antibody orientation is directly related to the local antibody concentration in the surrounding microenvironment, although the molecular mechanism for this phenomenon is not known. In this project, one of the two major forms of phagocytosis, antibody-mediated, will be characterized at a molecular level, with the ultimate goal of understanding the absolute molecular basis for the internalization process.

In this project the focus is on one group of pathogens – the Gram-positive cocci, a group of bacteria that includes some of the most important human pathogens, like group A, B and G streptococci, Staphylococcus aureus and Streptococcus pneumoniae. They account for the largest number of bacterial infections and deaths in the developed countries. A very interesting feature of these pathogens is that they are often present as a normal colonizers of mucosal surfaces and can cause many mild infections but are also the cause of many life-threatening disorders, such as sepsis, even in completely healthy individuals.

The methodology is based on quantitative approaches for flow cytometry, mass spectrometry and fluorescence microscopy. The phagocytic targets – beads and bacteria – will be characterized in detail with absolute quantification of important surface molecules such as IgG. Ultimately, a novel quantitative analysis approach will be developed improving assessment of phagocytosis in the field further.