Bacteria such as Chlamydia cause various diseases in humans and animals. Unlike extracellular bacteria, they invade, survive, and replicate inside host cells. Their development takes place within inclusions, membrane-bound compartments of cells. Chlamydiae induce cell-mediated immunity that begins with the action of dendritic cells. Dendritic cells take up antigens and process these for presentation to cytotoxic T cells. How antigens such as chlamydia are processed for T cell presentation is not well understood.
Intracellular protein debris and damaged organelles such as mitochondria are degraded by a processes of autophagy (mitophagy in the case of mitochondrial degradation). The degradation of invading organisms is termed xenophagy and involves the destruction of bacteria present in inclusions or vacuolar compartments. This destruction of bacteria in inclusions facilitates presentation to T cells. A group of scientists studied how dendritic cells degrade the chlamydial material via mito-xenophagy, and how they disturb chlamydial survival via a metabolic switch.
Laboratory mice, a bone marrow−derived mouse dendritic cell line, and a non-avian C. psittaci strain were used To infect Dendritic cells. The infected cells were analyzed by western blot and densitometry using antibodies against LC3 (to track the conversion of LC3-I to LC3-II which indicates autophagic activity). Results of this analysis showed that the degraded inclusions were targeted for autophagy in the dendritic cells. Knockdown of autophagy regulators (Beclin-1 and Atg7) using siRNA caused an increase in the number and bacterial load of chlamydia-infected dendritic cells, and T cell stimulation by these dendritic cells was reduced, further demonstrating the role of autophagy in dendritic cell Chlamydia defense.
A marker of mitochondrial damage (Pink-1) accumulated in Chlamydia-infected dendritic cells, and mitochondrial membrane breakdown was also evident when tracked using mitotracker staining. Using a fluorogenic probe and flow cytometry revealed removal of damaged mitochondria in the infected dendritic cells. This loss of mitochondria led to an increase in aerobic glycolysis without affecting ATP levels. Therefore, this metabolic switch from oxidative phosphorylation to glycolysis compensates for the cells’ loss of mitochondrial energy source, promotes dendritic cell survival, and deprives the pathogen of energy.
HemaCare offers top notch, customizable dendritic cells to further your research. Call us today at 877-397-3087 to speak with one of our specialists.
Radomski, N., Kägebein, D., Liebler-Tenorio, E., Karger, A., Rufer, E., & Tews, B. et al. (2017). Mito-xenophagic killing of bacteria is coordinated by a metabolic switch in dendritic cells. Scientific Reports, 7(1). doi:10.1038/s41598-017-04142-5