T cell-monocyte complexes in human blood hold molecular signatures of functional interactions

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B622
Abstract ID: 5522

Presenting Author:
Julie G Burel , Instructor at La Jolla Inst. for Immunol.

Abstract:

Physical communication between immune cells is a critical feature of immune responses. We have previously demonstrated the presence of T cell-monocyte complexes (i.e., a cell doublet pairing one T cell and one monocyte) in human blood samples analyzed by flow cytometry, with features suggesting biological association. Here we further dove into their biology, by performing a large-scale transcriptomic analysis of T cell-monocyte complexes isolated from individuals with active tuberculosis (ATB). We designed a two-step strategy where doublets were first isolated and cells physically detached from each other, followed by single-cell sequencing, thus bypassing the need for bioinformatic deconvolution. We also took leverage of the first high-throughput imaging cell sorter ever developed, the BD FACSDiscover S8 from BD Biosciences, to compare the molecular profile of doublets with synaptic vs coincidental contact. We found that the transcriptomic signature of synaptic complexes was associated with cytotoxicity, inflammation and MHC-II complex, and was more prominent at diagnosis compared to post-ATB treatment. Interestingly, we also found evidence for RNA and protein transfer between cells forming complexes, and similar signatures in T cell-monocyte complexes isolated from individuals with dengue fever. Thus, circulating T cell-monocyte complexes hold signatures of functional interactions and may be a useful biomarker to assess cell-cell interactions in vivo during infection.