A novel method for characterizing cell-cell interactions at single-cell resolution reveals unique signatures in blood T cell-monocyte complexes during infection

Kang, N.; Chawla, A.; Hillman, H.; Tippalagama, R.; Kim, C.; Mikulski, Z.; Seumois, G.; Vijayanand, P.; Scriba, T. J.; De Silva, A. D.; Balmaseda, A.; Harris, E.; Weiskopf, D.; Sette, A.; Lindestam Arlehman, C.; Peters, B.; Burel, J. G.

doi:10.1101/2024.09.20.612103

bioRxiv · 10.1101/2024.09.20.612103

A novel method for characterizing cell-cell interactions at single-cell resolution reveals unique signatures in blood T cell-monocyte complexes during infection

Kang, N.·Chawla, A.·Hillman, H.·Tippalagama, R.·Kim, C.·Mikulski, Z.·Seumois, G.·Vijayanand, P.·Scriba, T. J.·De Silva, A. D.·Balmaseda, A.·Harris, E.·Weiskopf, D.·Sette, A.·Lindestam Arlehman, C.·Peters, B.·Burel, J. G.

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Abstract

Communication between immune cells through direct contact is a critical feature of immune responses. Here, we developed a novel high-throughput method 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 unique transcriptomic signatures indicative of TCR/MCH-II immune synapses. Additionally, T cells in complexes showed enrichment for effector phenotypes, imaging and transcriptomic features of active TCR signaling, and increased immune activity at diagnosis compared to after anti-TB therapy. We also found evidence for bidirectional RNA exchange between T cells and monocytes, since complexes were markedly enriched for "dual-expressing" cells (i.e., co-expressing T cell and monocyte genes). Thus, studying immune cell complexes at a single-cell resolution offers novel perspectives on immune synaptic interactions occurring in blood during infection. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=59 SRC="FIGDIR/small/612103v1_ufig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@f90023org.highwire.dtl.DTLVardef@178007corg.highwire.dtl.DTLVardef@167e53corg.highwire.dtl.DTLVardef@1faff48_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Kang, N., Chawla, A., Hillman, H., Tippalagama, R., Kim, C., Mikulski, Z., Seumois, G., Vijayanand, P., Scriba, T. J., De Silva, A. D., Balmaseda, A., Harris, E., Weiskopf, D., Sette, A., Lindestam Arlehman, C., Peters, B., Burel, J. G.. 2024-09-23. A novel method for characterizing cell-cell interactions at single-cell resolution reveals unique signatures in blood T cell-monocyte complexes during infection. https://doi.org/10.1101/2024.09.20.612103

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