Coordinated host-pathogen transcriptional dynamics revealed using sorted subpopulations and single macrophages infected with Candida albicans

José F. Muñoz, Toni Delorey, Christopher B. Ford, Bi Yu Li, Dawn A. Thompson, Reeta P. Rao () and Christina A. Cuomo ()
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José F. Muñoz: Broad Institute of MIT and Harvard
Toni Delorey: Broad Institute of MIT and Harvard
Christopher B. Ford: Broad Institute of MIT and Harvard
Bi Yu Li: Broad Institute of MIT and Harvard
Dawn A. Thompson: Broad Institute of MIT and Harvard
Reeta P. Rao: Broad Institute of MIT and Harvard
Christina A. Cuomo: Broad Institute of MIT and Harvard

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-09599-8

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