The immune system protects us against disease through a variety of mechanisms that result in pathogen elimination. Host innate immune cells can control infections by activating NADPH oxidase, which generates reactive oxygen species (ROS) to kill pathogens directly. A defective NADPH oxidase leads to chronic granulomatous disease (CGD), which causes recurrent infections within the host. Autophagy, a cellular recycling pathway, can also target pathogens for destruction and may be a pathway that is compromised within a CGD patient. Recent work suggests that autophagy can be activated by ROS in vitro. By utilizing transparent zebrafish, we are able to characterize the role of ROS and autophagy in innate immunity during fungal infection with Candida albicans. We administered DPI, α-tocopherol, and PMA to infected zebrafish to alter the levels of ROS then quantified the effects on autophagy using confocal microscopy. Our data suggests differences in autophagy activation in vivo. Additionally, we were able to enhance our understanding of loose phagosomes and provide a possible physiological difference between tight and loose phagosome morphologies. Further research is required in order to confirm new hypotheses regarding interactions between ROS and cell receptor signaling pathways that might activate autophagy and reasons for the distinct dichotomy of phagosomes observed within a live vertebrate host.
Norum, Ashley E., "The Role of Reactive Oxygen Species in Autophagy Activation During Candida albicans Infection" (2012). Honors College. 70.