Mycobacterium tuberculosis infection drives a type I IFN signature in lung lymphocytes

Mycobacterium tuberculosis (Mtb) infects 25% of the world???s population and causes tuberculosis (TB), which is a leading cause of death globally. A clear understanding of the dynamics of immune response at the cellular level is crucial to design better strategies to control TB. We use the single-cell RNA sequencing approach on lung lymphocytes derived from healthy and Mtb-infected mice. Our results show the enrichment of the type I IFN signature among the lymphoid cell clusters, as well as heat shock responses in natural killer (NK) cells from Mtb-infected mice lungs. We identify Ly6A as a lymphoid cell activation marker and validate its upregulation in activated lymphoid cells following infection. The cross-analysis of the type I IFN signature in human TB-infected peripheral blood samples further validates our results. These findings contribute toward understanding and characterizing the transcriptional parameters at a single-cell depth in a highly relevant and reproducible mouse model of TB.

Automated summary

Using single-cell RNA sequencing, this study reveals the enrichment of type I interferon signature and heat shock responses in lymphoid cell clusters and natural killer cells from Mycobacterium tuberculosis-infected mouse lungs. Ly6A is identified as a lymphoid cell activation marker, and its upregulation in activated lymphoid cells following infection is confirmed. Cross-analysis of type I interferon signature in human TB-infected peripheral blood samples further validates these findings.