Concordant and discordant gene expression patterns in mouse strains identify best-fit animal model for human tuberculosis

Abstract Immunity in infection, inflammation and malignancy differs markedly in man and mouse. Still, we learn about human immunity in large extent from experimental mouse models. We propose a novel data integration approach which identifies concordant and discordant gene expression patterns of the immune responses in heterologous data sets. We have conducted experiments to compare human and murine transcriptional responses to Mycobacterium tuberculosis (Mtb) infection in whole blood (WB) as well as macrophages and compared them with simulated as well as publicly available data. Our results indicate profound differences between patterns of gene expression in innate and adaptive immunity in man and mouse upon Mtb infection. We characterized differential expression of T-cell related genes corresponding to the differences in phenotype between tuberculosis (TB) highly and low susceptible mouse strains. Our approach is general and facilitates the choice of optimal animal model for studies of the human immune response to a particular disease

The Henna pigment Lawsone activates the Aryl Hydrocarbon Receptor and impacts skin homeostasis

As a first host barrier, the skin is constantly exposed to environmental insults that perturb its integrity. Tight regulation of skin homeostasis is largely controlled by the aryl hydrocarbon receptor (AhR). Here, we demonstrate that Henna and its major pigment, the naphthoquinone Lawsone activate AhR, both in vitro and in vivo. In human keratinocytes and epidermis equivalents, Lawsone exposure enhances the production of late epidermal proteins, impacts keratinocyte differentiation and proliferation, and regulates skin inflammation. To determine the potential use of Lawsone for therapeutic application, we harnessed human, murine and zebrafish models. In skin regeneration models, Lawsone interferes with physiological tissue regeneration and inhibits wound healing. Conversely, in a human acute dermatitis model, topical application of a Lawsone-containing cream ameliorates skin irritation. Altogether, our study reveals how a widely used natural plant pigment is sensed by the host receptor AhR, and how the physiopathological context determines beneficial and detrimental outcomes