Single-Cell RNA Sequencing to Understand Host–Pathogen Interactions

Host–pathogen interactions, particularly in the context of bacterial infections, are dynamic exchanges where transcriptional heterogeneity from both the host and the pathogen can lead to many diverse outcomes via distinct molecular pathways. Transcriptional profiling at the single-cell level, on a genome-wide scale, has enabled a greater appreciation of the cellular diversity in complex biological organisms and the myriad of host transcriptional states during infection. Here, we highlight recent reports of single-cell RNA sequencing within the context of host–pathogen interactions, describe current limitations for detecting and profiling the transcriptome of invading pathogens at the single-cell level, and suggest exciting future prospects for this technology in the study of infection. We propose that understanding infection as an integrated process between pathogen and host with resolution at the single-cell level will ultimately inform development of vaccines with greater productive and protective host immunity, enable the development of novel therapeutics that harness host mechanisms, and yield more accurate biomarkers to guide better diagnostics.