University of Cambridge > Talks.cam > Immunology in Pathology > Innate crosstalk of unconventional T cells, monocytes and neutrophils in bacterial infection

Innate crosstalk of unconventional T cells, monocytes and neutrophils in bacterial infection

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If you have a question about this talk, please contact Sue Griffin.

Host: John Trowsdale (jt233@cam.ac.uk)

Unconventional T-cells such as human blood γδ T-cells and MAIT cells, monocytes and neutrophils share a responsiveness toward inflammatory stimuli and rapidly accumulate at sites of infection. Studying their interaction in vitro and relating these findings to in vivo observations in patients therefore provides crucial insight into inflammatory events.

Our data demonstrate that human γδ T-cells and MAIT cells readily respond to neutrophils harboring phagocytosed bacteria, as evidenced by expression of activation markers and secretion of pro-inflammatory cytokines. This response appears to be dependent on the ability of these bacteria to produce metabolites of the microbial non-mevalonate isoprenoid pathway and the vitamin B2 pathway, and requires cell-cell contact with accessory monocytes. In turn, both types of unconventional T-cells provide potent survival signals resulting in monocyte and neutrophil activation and differentiation. We believe that the stimulation of unconventional T-cells at the site of infection amplifies the inflammatory response and has important consequences for pathogen clearance and the development of microbe-specific immunity.

However, if triggered at the wrong time or the wrong place, this rapid reaction toward bacteria may also lead to inflammation-related damage. For instance, patients with acute peritoneal-dialysis (PD)-associated bacterial peritonitis – characterized by an excessive influx of neutrophils and monocytes into the peritoneal cavity – show a selective activation of local γδ T-cells depending on the presence of the non-mevalonate pathway in the causative bacterial pathogens. We find a similar activation of circulating γδ T-cells in patients with acute sepsis. In both diseases, the γδ T cell-driven perpetuation of inflammatory responses is associated with detrimental clinical outcomes.

Our findings indicate a direct link between invading pathogens, neutrophils, monocytes and microbe-responsive unconventional T-cells in early infection, and suggest novel diagnostic and therapeutic approaches.

This talk is part of the Immunology in Pathology series.

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