Aluminium based adjuvants and their effects on mitochondria and lysosomes of phagocytosing cells

•Increased mitochondrial activity and production of reactive oxygen species (ROS).•Obstructed formation of acidic vesicles•An almost complete inhibition of cathepsin L activity, a cysteine proteinase of the phagolysomes.

Aluminium oxyhydroxide, Al(OH)3 is one of few compounds approved as an adjuvant in human vaccines. However, the mechanism behind its immune stimulating properties is still poorly understood. In vitro co-culture of an aluminium adjuvant and the human monocytic cell line THP-1 resulted in reduced cell proliferation. Inhibition occurred at concentrations of adjuvant several times lower than would be found at the injection site using a vaccine formulation containing an aluminium adjuvant. Based on evaluation of the mitochondrial membrane potential, THP-1 cells showed no mitochondrial rupture after co-culture with the aluminium adjuvant, instead an increase in mitochondrial activity was seen. The THP-1 cells are phagocytosing cells and after co-culture with the aluminium adjuvant the phagosomal pathway was obstructed. Primary or early phagosomes mature into phagolysosomes with an internal pH of 4.5 – 5 and carry a wide variety of hydrolysing enzymes. Co-culture with the aluminium adjuvant yielded a reduced level of acidic vesicles and cathepsin L activity, a proteolytic enzyme of the phagolysosomes, was almost completely inhibited. THP-1 cells are an appropriate in vitro model in order to investigate the mechanism behind the induction of a phagocytosing antigen presenting cell into an inflammatory cell by aluminium adjuvants. Much information will be gained by investigating the phagosomal pathway and what occurs inside the phagosomes and to elucidate the ultimate fate of phagocytosed aluminium particles.

Graphical abstractPhagocytosis of aluminium adjuvant particles by the human monocytic cell line THP-1. Cells were incubated with aluminium adjuvant containing adsorbed fluorescence labelled ovalbumin. After  incubation at 37 °C the cells were washed and inspected by;A.Light microscopeB.Fluorescence microscope:Green fluorescence: ovalbumin/aluminium particles.Blue fluorescence: nuclei stain DAPI.Figure optionsDownload full-size imageDownload as PowerPoint slide