Summary

Complex interactions between different host immune cell types can determine the outcome of pathogen infections. Advances in single cell RNA-sequencing (scRNA-seq) allow probing of these immune interactions, such as cell-type compositions, which are then interpreted by deconvolution algorithms using bulk RNA-seq measurements. However, not all aspects of immune surveillance are represented by current algorithms. Here, using scRNA-seq of human peripheral blood cells infected with Salmonella, we develop a deconvolution algorithm for inferring cell-type specific infection responses from bulk measurements. We apply our dynamic deconvolution algorithm to a cohort of healthy individuals challenged ex vivo with Salmonella, and to three cohorts of tuberculosis patients during different stages of disease. We reveal cell-type specific immune responses associated not only with ex vivo infection phenotype but also with clinical disease stage. We propose that our approach provides a predictive power to identify risk for disease, and human infection outcomes.

Overall design

Frozen PBMCs from healthy individual were defrosted and infected ex vivo with Salmonella enterica serovar Typhimurium.

Contributors

Noa Bossel Ben-Moshe 1, Shelly Hen-Avivi 1, Natalia Levitin 1, Dror Yehezkel 1, Marije Oosting 2, Leo A B Joosten 2, Mihai G Netea 2 3, Roi Avraham 4

Contact

roi.avraham@weizmann.ac.il.(Roi Avraham)