GSE200639
Mycobacterium tuberculosis infection drives a Type I IFN signature in lung lymphocytes
Mycobacterium tuberculosis (Mtb) infects a quarter 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 cellular level is crucial to design better strategies to control TB. We have employed single-cell RNA-seq approach on lung lymphocytes derived from healthy and Mtb-infected mice. Our results show enrichment of type I IFN responsive phenotypes among the lymphoid cell clusters, as well as heat shock responses in natural killer (NK) cells from Mtb-infected mice lungs. We have identified Ly6A as a novel lymphoid cell activation marker and validated its upregulation in activated lymphoid cells post Mtb infection. The cross analysis of type I IFN signature in human TB infected peripheral blood samples further validates our results. These findings significantly contribute toward understanding and characterizing the transcriptional parameters at single-cell depth in a highly relevant and reproducible mouse model of TB. Overall design: To characterize the lung lymphocyte landscape of mice infected with low dose Mtb, we performed 10x scRNA-seq on single-cells from the lungs of control (uninfected, n = 2), 50 days post-infection (dpi) (D50 Inf, n = 3), and 100 dpi (D100 Inf, n = 3) mice