Coordinated host-pathogen transcriptional dynamics revealed using sorted subpopulations and single macrophages infected with Candida albicans.
Jose F MuñozToni Marie DeloreyChristopher B FordBi Yu LiDawn A ThompsonReeta P RaoChristina A CuomoPublished in: Nature communications (2019)
The outcome of fungal infections depends on interactions with innate immune cells. Within a population of macrophages encountering Candida albicans, there are distinct host-pathogen trajectories; however, little is known about the molecular heterogeneity that governs these fates. Here we developed an experimental system to separate interaction stages and single macrophage cells infected with C. albicans from uninfected cells and assessed transcriptional variability in the host and fungus. Macrophages displayed an initial up-regulation of pathways involved in phagocytosis and proinflammatory response after C. albicans exposure that declined during later time points. Phagocytosed C. albicans shifted expression programs to survive the nutrient poor phagosome and remodeled the cell wall. The transcriptomes of single infected macrophages and phagocytosed C. albicans displayed a tightly coordinated shift in gene expression co-stages and revealed expression bimodality and differential splicing that may drive infection outcome. This work establishes an approach for studying host-pathogen trajectories to resolve heterogeneity in dynamic populations.
Keyphrases
- candida albicans
- gene expression
- single cell
- biofilm formation
- induced apoptosis
- cell wall
- poor prognosis
- cell cycle arrest
- depressive symptoms
- immune response
- transcription factor
- endoplasmic reticulum stress
- hiv infected
- public health
- binding protein
- adipose tissue
- oxidative stress
- signaling pathway
- cystic fibrosis
- pseudomonas aeruginosa
- heat shock
- heat shock protein
- genetic diversity