Pioneering single-cell intracellular metagenomics: a revolutionary new window into microbe-immune interactions at barrier tissues.

Our skin and gut house multitudes of bacteria that influence our health via interactions with key immune sentinel cells that engulf these microbes and respond dynamically to their signals. Previously we have had to rely heavily on animal models to try to decode this language between our immune sentials and the bacteria they sense, because we have lacked to tools to meaningfully capture the relevant information from human tissues. To overcome this hurdle we have recently developed a novel single-cell genomic method for simulatenously capturing and sequencing DNA from both these immune sentinel cells and the bacteria they contain, therby providing us with an unprecendented view into the nature of these bacteria-immune cell interactions. By applying this novel approach to samples of healthy human skin and gut, we hope to shed new light on how helpful and harmful bacteria are sensed at these barrier tissues, how the immune system decides when (and what) to attack, and the molecular and cellular cues that guide these decisions. These studies will transform our understanding of bacterial influences on our health and set the stage for future work to interrogate their role in specific human diseases such as Inflammatory Bowel Disease.