Understanding the pathogenesis of infectious diseases by single-cell RNA sequencing

Abstract

Infections are highly orchestrated and dynamic processes, which involve both pathogen and host. Transcriptional profiling at the single-cell level enables the analysis of cell diversity, heterogeneity of the immune response, and detailed molecular mechanisms underlying infectious diseases caused by bacteria, viruses, fungi, and parasites. Herein, we highlight recent remarkable advances in single-cell RNA sequencing (scRNA-seq) technologies and their applications in the investigation of host-pathogen interactions, current challenges and potential prospects for disease treatment are discussed as well. We propose that with the aid of scRNA-seq, the mechanism of infectious diseases will be further revealed thus inspiring the development of novel interventions and therapies.

Keywords: bacteria; fungi; immune response; infectious diseases; parasites; single-cell RNA sequencing; viruses.

Figure 1. FIGURE 1: Risk factors, vulnerable organs and cell types involved in SARS-Cov-2 infection.

Single-cell RNA-seq revealed high expression of ACE2 and TMPRSS2 in multiple organs and cell types, which are more vulnerable to SARS-Cov-2 infection. Several factors play important roles in infection and disease process, such as age, smoking and gender.

Figure 2. FIGURE 2: Using single-cell RNA-seq to understand host-pathogen interactions.

Pathogens like bacteria, viruses, fungi and parasites can infect hosts and cause various infectious diseases (A). Using scRNA-seq methods enable the study of host and pathogen interactions at a high-resolution level (B-C). The single cell transcriptomes reveal the differentially gene expression map during infection (D), demonstrate the cell heterogeneity and immune cell development (E), uncover the mechanism behind the inflammatory and anti-microbial response (F). The application of scRNA-seq highly contributes to infection research.