T cell monocyte complexes exhibit distinct immune signatures during infection.

Communication between immune cells through direct contact is a critical feature of immune responses. Here, we developed an innovative high-throughput workflow to study the transcriptome and adaptive immune receptor repertoire of single cells forming complexes without needing bioinformatic deconvolution. We found that T cells and monocytes forming complexes in blood during active tuberculosis (TB) and dengue hold distinct transcriptomic signatures from singlets, with the upregulation of genes associated with immune activation and MHC-II complex. Additionally, in TB, T cells in complexes showed enrichment for cytotoxic T cells, higher TCR clonality, and increased immune activity at diagnosis compared to after anti-TB therapy. We also found that T cells and monocytes forming complexes were markedly enriched for "dual-expressing" cells (i.e., co-expressing T cell and monocyte genes), suggesting intercellular RNA acquisition occurs during cell-cell interactions. Thus, studying immune cell complexes at single-cell resolution provides insights into immune cell-cell interactions in the blood during infection.