Oral Presentation Lorne Infection and Immunity 2019

Battle to the end: how the interplay of host and pathogen metabolism regulates innate immune interactions in fungal infections (#26)

Ana Traven 1
  1. Monash University, Clayton, VIC, Australia

Fungal pathogens cause millions of human infections every year, ranging from skin and nail infections to invasive, deadly fungal diseases that kill more than 1.5 million people per year according to estimates. Antifungal treatment options are few, and antimicrobial drug resistance (AMR) is a problem, including the recent emergence of the fungal superbug Candida auris. Our focus is on Candida albicans, a yeast that lives commensally with humans, but which can cause infections, both mucosal and systemic, when immune defences or competing microbiota are compromised. Innate immune phagocytes play important roles in anti-Candida defences. However, Candida can mount a counter-attack, with a key contributing mechanism relating to the transition between two morphological states, round yeast and filamentous hyphae. The formation of hyphal cells is linked to pathogenesis and escape from macrophages, but, paradoxically, hyphae are also recognised by immune cells to initiate defensive inflammatory programs. Therefore, a sophisticated interplay between these processes is likely to dictate the outcomes of fungal infections. We are combining fungal genetics and cell biology, live cell imaging of infected immune cells, “omics” approaches and animal infection models to dissect the interaction of C. albicans with innate immune cells. We want to understand who wins (host or pathogen?), when and why. Our specific interest is in deciphering how the metabolic interactions that result from immuno-metabolic shifts in host cells and metabolic reprogramming of the pathogen regulate viability of immune cells and microbes, host antimicrobial responses and pathogen evasion strategies.