Tuberculosis-associated IFN-I induces Siglec-1 on microtubule-containing tunneling nanotubes and favors HIV-1 spread in macrophages

To understand the susceptbility of human M(IL-10) macrophages to human immunodeficiency virus, we performed a genome-wide transcriptome analysis in these cells to identify a gene profile responsible for this phenomenon. A distinct 60 gene-transcript signature was defined in M(IL-10) macrophages, using a combination of the expression level, statistical filters and hierarchical clustering; 51 genes were up-regulated and 9 genes were down-regulated in M(IL-10) macrophages compared to control cells. Among the genes upregulated, we identified a interferon-stimulated gene (ISG) signature include SIGLEC-1. We confirmed SIGLEC-1 and other five ISG genes by qPCR, FACS and western blot. Human macrophages were diffentiated from freshly isolated monocytes treated with M-CSF and conditioned media. Conditioned media was generated from Mycobacterium tuberculosis-infected (coMtb) or non-infected (coCtrl) macrophages. Upon confirmation of the M(IL-10) macrophage phenotype induced by coMtb, and susceptbility to HIV-1 infectiion, the transcriptome analyses was performed in these conditioned cells from four independent donors.