Spatial whole transcriptome analysis (GeoMx; Nanostring) of cervical lymph nodes (cLNs) from C57BL/6 mice infected intradermally (i.d.) with Mycobacterium tuberculosis (Mtb) reveals transcriptional changes at the edge of lesions.

Here, we used a mouse model of latent lymphatic M. tuberculosis (Mtb) infection (LTBI) to dissect the immunological mechanisms underlying LTBI containment versus reactivation. We show that immunosuppression-mediated reactivation of lymphatic LTBI and the subsequent induction of progressive disease can be prevented by vaccination with BCG or recombinant BCG (BCG::ESAT-6-PE25SS (abbreviated to PE25) even in the absence of CD4+ T cells. Spatial transcriptomics, network analysis and bioinformatic reveal that anti-CD4-mediated immunosuppression is associated with and enhanced immune response at the edge of TB lesions within the infection-draining cervical lymph nodes. Overall design: 30 Regions of Interest (ROI) including 3 different tissue lesions of cLNs were analysed. Treament groups included are 1) untreated mice (Normal); 2) unvaccinated and Mtb-infected (Mtb); 3) unvaccinated, immunosuppressed with anti-CD4 mAb and Mtb-infected (Mtb+aCD4); 4) vaccinated with BCG, immunosuppressed with anti-CD4 mAb and Mtb-infected (BCG+aCD4+Mtb); 5) vaccinated with PE25, immunosuppressed with anti-CD4 mAb and Mtb-infected (PE25+aCD4+Mtb). Each treated group included different ROI types (Normal in naive or normal in disease, Lesion and Edge of Lesion).