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

结核分枝杆菌感染驱动肺淋巴细胞中I型干扰素的特征表达

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作者:Sadia Akter ,Kuldeep S Chauhan ,Micah D Dunlap ,José Alberto Choreño-Parra ,Lan Lu ,Ekaterina Esaulova ,Joaquin Zúñiga ,Maxim N Artyomov ,Deepak Kaushal ,Shabaana A Khader

Abstract

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.

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