Vizgen MERFISH files for Single-cell analysis reveals M. tuberculosis ESX-1-mediated accumulation of anti-inflammatory macrophages in infected mouse lungs

Mycobacterium tuberculosis (MTB) ESX-1, a type VII secretion system, is a
key virulence determinant contributing to MTB’s survival within lung
mononuclear phagocytes (MNPs), but its effect on MNP recruitment and
differentiation remains unknown. Here, using multiple single-cell RNA
sequencing techniques, we studied the role of ESX-1 in MNP heterogeneity
and response in mice and murine bone marrow-derived macrophages (BMDM). We
found that ESX-1 is required for MTB to recruit diverse MNP subsets with
high MTB burden. Further, MTB induces an anti-inflammatory transcriptional
signature in MNPs and BMDM in an ESX-1-dependent manner.  Spatial
transcriptomics revealed an upregulation of anti-inflammatory signals
within MTB lesions, where monocyte-derived macrophages concentrate near
MTB-infected cells. Together, our findings suggest that MTB ESX-1
facilitates the recruitment and differentiation of anti-inflammatory MNPs,
which MTB can infect and manipulate for survival. Importantly, we provide
a comprehensive transcriptomic dataset across various models and methods,
which could contribute to the broader understanding of recruited cell
heterogeneity during MTB lung infection. This data is associated with
processed data and code found
in https://doi.org/10.5061/dryad.0p2ngf28s.