ABSTRACT
Intestinal epithelial cell (IEC) NF-κB signaling regulates the balance between mucosal homeostasis and inflammation. It is not fully understood which signals tune this balance and how bacterial exposure elicits the process. Pure LPS induces epithelial NF-κB activation in vivo. However, we found that in mice, IECs do not respond directly to LPS. Instead, tissue-resident lamina propria intercrypt macrophages sense LPS via TLR4 and rapidly secrete TNF to elicit epithelial NF-κB signaling in their immediate neighborhood. This response pattern is relevant also during oral enteropathogen infection. The macrophage-TNF-IEC axis avoids responses to luminal microbiota LPS but enables crypt- or tissue-scale epithelial NF-κB responses in proportion to the microbial threat. Thereby, intercrypt macrophages fulfill important sentinel functions as first responders to Gram-negative microbes breaching the epithelial barrier. The tunability of this crypt response allows the induction of defense mechanisms at an appropriate scale according to the localization and intensity of microbial triggers.
Subject(s)
Anti-Bacterial Agents/metabolism , Epithelial Cells/metabolism , Intestinal Mucosa/metabolism , Intestines/metabolism , NF-kappa B/metabolism , Tumor Necrosis Factors/metabolism , Animals , Gene Expression Regulation/physiology , Inflammation/metabolism , Macrophages/drug effects , Mice , Mice, Inbred C57BL , Signal Transduction/physiologyABSTRACT
In order to prevent microbial contamination of food, monitoring of the production environment, together with the rapid detection of foodborne pathogens have proven to be of utmost importance for Food Safety. Environmental monitoring should detect harmful pathogens at the earliest point in time in order for the necessary interventions to be taken. However, current detection methods fall short with regards to speed, ease of use, and cost. This article aims to present the idea behind NEMIS Technologies, a startup company making use of the novel AquaSparkTM technology for the development of a new generation of bacterial detection methods. These methods utilize chemiluminescence in order to detect live target bacteria in a short period of time compared to that of conventional methods. We show that dry-stressed Listeria monocytogenes can be detected within 24 hours, using small-molecule chemiluminescent probes, together with a bacteria-specific proprietary enrichment broth containing a cocktail of bacteriophages, which enhance the specificity and sensitivity. This novel platform technology has the potential to extend beyond environmental monitoring towards food analyses as well as veterinary and human health.
