How do human epidermal Langerhans cells facilitate the recognition, differentiation, and tissue response to different Staphylococci?

How does skin, our largest immunological organ, live in harmony with it’s diverse microflora yet also react to bacterial pathogens?

Here we utilize cutting-edge human skin models, bacterial strains and immunological tools to understand how human skin differentiates bacterial friend from foe.

We recently showed that human Langerhans cells (LCs) differentiate between commensal (Staphylococcus epidermidis) and pathogenic (methicillin resistant S. aureus – MRSA) bacteria via IL-1ß signaling in situ.

To expand these findings, this project sets out to (1) visualize the in situ activation and migratory behavior of LCs exposed to Staphylococci. (2) Identify the different inflammatory signals which delineate the LC and skin response to friend or foe. (3) Use single cell RNA-sequencing to identify the transcriptional profiles of individual cells in the skin, looking for cellular sub-sets and evidence of immunogenic vs immunotolerant shifts in these populations. (4) Finally, we will use Spatial Transcriptomics to localize these signals within the skin tissue, examining the role of cell-cell interactions and skin structural features.

This work will give unprecedented resolution to the human skin response to bacteria and how these responses differ dependent on bacterial properties.

Understanding the underlying defense and tolerance mechanisms of our skin will identify new targets for boosting immunity and mounting an effective response against antibiotic resistant bacteria.