No abstract

Autosomal dominant hyper IgE syndrome (AD-HIES), or Job's syndrome, is a primary immune deficiency caused by dominant-negative mutations in STAT3. Recurrent Staphylococcus aureus skin abscesses are a defining feature of this syndrome. A widely held hypothesis that defects in peripheral Th17 differentiation confer this susceptibility has never been directly evaluated. To assess the cutaneous immune response in AD-HIES, we induced suction blisters in healthy volunteers (HVs) and patients with AD-HIES and then challenged the wound with lethally irradiated bacteria. We show that cutaneous production of IL-17A and IL-17F was normal in patients with AD-HIES. Overproduction of TNF-α differentiated the responses in AD-HIES from HVs. This was associated with reduced IL-10 family signaling in blister-infiltrating cells and defective epithelial cell function. Mouse models of AD-HIES recapitulated these aberrant epithelial responses to S. aureus and involved defective epithelial-to-mesenchymal transition (EMT) rather than a failure of bacterial killing. Defective responses in mouse models of AD-HIES and primary keratinocyte cultures from patients with AD-HIES could be reversed by TNF-α blockade and by drugs with reported modulatory effects on EMT. Our results identify these as potential therapeutic approaches in patients with AD-HIES suffering S. aureus infections.

Author response.

Under a traditional paradigm, only those with the expected background knowledge consume academic literature. The lay press, as well as government and non-government agencies, play a complementary role of extracting findings of high interest or importance and translating them for general viewing. The need for accurate reporting and public advising is paramount when attempting to tackle epidemic outbreaks through behavior change. Yet, public trust in media outlets is at a historic low. The Crisis and Emergency Risk Communication (CERC) model for media reporting on public health emergencies was established in 2005 and has subsequently been used to analyze media reporting on outbreaks of influenza and measles as well as smoking habits and medication compliance. However, no media analysis had yet been performed on the 2013–2016 Ebola Virus Disease (EVD) outbreak. This study compared the EVD information relayed by lay press sources with general review articles in the academic literature through a mixed-methods analysis. These findings suggest that comprehensive review articles could not serve as a source to clarify and contextualize the uncertainties around the EVD outbreak, perhaps due to adherence to technical accuracy at the expense of clarity within the context of outbreak conditions. This finding does not imply inferiority of the academic literature, nor does it draw direct causation between confusion in review articles and public misunderstanding. Given the erosion of the barriers siloing academia, combined with the demands of today’s fast-paced media environment, contemporary researchers should realize that no study is outside the public forum and to therefore consider shifting the paradigm to take personal responsibility in the process of accurately translating their scientific words into public policy actions to best serve as a source of clarity.