Modulation of the antibody response can influence the immune response more than previously thought, and also can better direct complement deposition. Cooperation between opsonins is therefore a fundamental aspect to be considered in the development of future anti-infectious strategies. This was concluded by Elena Boero who defended her PhD thesis on January 13 in Utrecht.

Phagocytosis is an indispensable defense mechanism against bacterial infections. Molecules such as antibodies and complement proteins are essential to make phagocytosis as effective as possible; without them, the recognition of pathogenic bacteria by phagocytes would be severely limited. In her thesis, Elena Boero (Department of Medical Microbiology, UMC Utrecht and GSK Vaccines, Siena, Italy) and colleagues have investigated the role of opsonins (extracellular proteins that, when tagged to substances or cells, induce phagocytes) in bacterial phagocytosis, both individually and in combination.

Phagocytosis model

In a reductive phagocytosis model, the investigators have shown that the complement protein C3b alone mediates the phagocytosis of bacteria, in contrast to the widespread idea that antibodies or other types of stimuli are essential to assist the phagocyte’s activation. They have also seen how antibodies without complement induce modest phagocytosis of S. aureus. However, its effectiveness can be increased by selecting a convenient combination of bacterial target and effector tail. The IgG3 anti-SpA antibodies mediate sufficient phagocytosis of S. aureus, despite the immune evasion action of protein A.

Cooperation

Although each opsonin can be used separately, the cooperation between antibodies and complement proteins is essential to achieve the maximum efficacy of phagocytosis. Antibodies ensure specific bacterium recognition and provide the basis for optimal complement deposition. On the other hand, the complement system helps to destroy bacteria and acquire new information to improve the specificity of antibodies.

Elena Boero concluded: “Through vaccination or the use of therapeutic monoclonal antibodies, we have the opportunity to intervene on phagocytosis, strengthening it against our bacteria of interest. In fact, by modulating the antibody response, we can influence the immune response much more than we imagined, and better direct complement deposition. Cooperation between opsonins is therefore a fundamental aspect to be considered in the development of all future anti-infectious strategies.”

PhD defense

Elena Boero (1993, Genoa, Italy) defended her PhD thesis on January 13, 2022 at Utrecht University. The title of her thesis is “How opsonins drive bacterial uptake – a phagocytes dinner”. Supervisors were prof. dr. Jos van Strijp and prof. dr. Suzan Rooijakkers (both Department of Medical Microbiology, UMC Utrecht). Co-supervisor was dr. Kok van Kessel (Department of Medical Microbiology, UMC Utrecht). As of January 2022, Elena Boero works as a postdoctoral researcher at GSK Vaccines, Siena, Italy.