Madhu Shankar and Ana Traven
Infection and Immunity Program and the Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University
Abstract
Candida albicansis one of the most important fungal pathogens. C. albicansis a commensal organism, but in immunosuppressed hosts it can cause life-threatening infections. The initial and crucial defense mechanisms against C. albicansare orchestrated by innate-immune phagocytes, with neutrophils being a very potent killer of this fungus by oxidative mechanisms and through the production of neutrophil extracellular traps (NETs) that can destroy large fungal filaments. A limitation of the studies to date is that neutrophil responses to C. albicanshave been addressed using only a limited number of clinical isolates. Therefore, little is known about potentially distinct interactions by diverse clinical strains. In other words, we have poor understanding of how generalizable our current knowledge of Candida-neutrophil interactions is. To address this key question, we are using a panel of diverse clinical C. albicansisolates and performing a detailed analysis of their interactions with human neutrophils. We are focusing on the ability of the pathogen to induce reactive oxygen species (ROS) and NET formation, and survive the attempts of neutrophils to kill them. In our initial study of 8 clinical isolates we found differences in the mentioned neutrophil responses compared to the commonly used, highly virulent clinical C. albicansisolate SC5314. Our current studies are aimed at understanding if the nature of the interaction of C. albicans with neutrophils dictates how the different clinical isolates are able to evade innate immunity and exist in commensal and/or pathogenic states.