Alex Ballesteros
Research Mentor(s): Kristie Goughenour
Department or Program: Internal Med, Microbiology & Immunology
Authors: A. Ballesteros, M. Lintner,Y. Sinitsya, K., Hissong, H. Lee, J. Xu, J. Tenor, J. Perfect, M. Olszewski, K. Goughenour
Session: Session 1: 12:00pm-12:50pm
Poster: 9
Abstract
Fungal diseases affect immunocompromised patients at an alarming rate, with unacceptably high mortality rates. A potential therapeutic target identified in the fungal pathogen Cryptococcus neoformans (C. neo), Trehalose-6-Phosphate (TPS1), plays a critical role in established virulence. TPS1 is an essential precursor to Trehalose, a disaccharide used by the fungus for a variety of applications. Recently we found that the loss of trehalose caused reduced capsule size in the tps1Δ. Decreased capsule resulted in an increase in the innate immune response and avirulence in a murine model. In a pulmonary model, mice infected with TPS1 deficient C. neo were able to clear the infection around 7-days post infection, while mice infected with the TPS1-sufficient (WT) strain reached endpoint criteria between day-14 and day-15 post infection. In this study we investigated the role of the innate immune response in fungal control of the tps1Δ mutant. Flow cytometry analysis showed increased neutrophil recruitment in tps1Δ infected mice. In vitro killing assays showed that tps1Δ mutant cells were more susceptible to killing by neutrophils compared to WT when serum was present, indicating a significant role for TPS1 in the protection of the fungi against neutrophil-mediated defenses. In our pulmonary infections model, mice with neutrophils depleted by anti-Ly6G treatment showed higher fungal burdens of the tps1Δ mutant on 2dpi compared to mice with neutrophils present. Thus neutrophils appear to be the major innate immune cell contributing to host control of the tps1Δ mutant.
