Production of IFN-β during Listeria monocytogenes Infection Is Restricted to Monocyte/Macrophage Lineage

The family of type I interferons (IFN), which consists of several IFN-α and one IFN-β, are produced not only after stimulation by viruses, but also after infection with non-viral pathogens. In the course of bacterial infections, these cytokines could be beneficial or detrimental. IFN-β is the primary member of type I IFN that initiates a cascade of IFN-α production. Here we addressed the question which cells are responsible for IFN-β expression after infection with the intracellular pathogen Listeria monocytogenes by using a genetic approach. By means of newly established reporter mice, maximum of IFN-β expression was observed at 24 hours post infection in spleen and, surprisingly, 48 hours post infection in colonized cervical and inguinal lymph nodes. Colonization of lymph nodes was independent of the type I IFN signaling, as well as bacterial dose and strain. Using cell specific reporter function and conditional deletions we could define cells expressing LysM as the major IFN-β producers, with cells formerly defined as Tip-DCs being the highest. Neutrophilic granulocytes, dendritic cells and plasmacytoid dendritic cells did not significantly contribute to type I IFN production

NOD2, RIP2 and IRF5 Play a Critical Role in the Type I Interferon Response to Mycobacterium tuberculosis

While the recognition of microbial infection often occurs at the cell surface via Toll-like receptors, the cytosol of the cell is also under surveillance for microbial products that breach the cell membrane. An important outcome of cytosolic recognition is the induction of IFNα and IFNβ, which are critical mediators of immunity against both bacteria and viruses. Like many intracellular pathogens, a significant fraction of the transcriptional response to Mycobacterium tuberculosis infection depends on these type I interferons, but the recognition pathways responsible remain elusive. In this work, we demonstrate that intraphagosomal M. tuberculosis stimulates the cytosolic Nod2 pathway that responds to bacterial peptidoglycan, and this event requires membrane damage that is actively inflicted by the bacterium. Unexpectedly, this recognition triggers the expression of type I interferons in a Tbk1- and Irf5-dependent manner. This response is only partially impaired by the loss of Irf3 and therefore, differs fundamentally from those stimulated by bacterial DNA, which depend entirely on this transcription factor. This difference appears to result from the unusual peptidoglycan produced by mycobacteria, which we show is a uniquely potent agonist of the Nod2/Rip2/Irf5 pathway. Thus, the Nod2 system is specialized to recognize bacteria that actively perturb host membranes and is remarkably sensitive to mycobacteria, perhaps reflecting the strong evolutionary pressure exerted by these pathogens on the mammalian immune system

Data analytics in a privacy-concerned world

Data is considered the new oil of the economy, but privacy concerns limit their use, leading to a widespread sense that data analytics and privacy are contradictory. Yet such a view is too narrow, because firms can implement a wide range of methods that satisfy different degrees of privacy and still enable them to leverage varied data analytics methods. Therefore, the current study specifies different functions related to data analytics and privacy (i.e., data collection, storage, verification, analytics, and dissemination of insights), compares how these functions might be performed at different levels (consumer, intermediary, and firm), outlines how well different analytics methods address consumer privacy, and draws several conclusions, along with future research directions

Tilt and decentration tolerance of intraocular lenses: Measurements with an improved mechanical model eye

Cataract, a clouding of the crystalline eye lens, is the leading cause of blindness. It can effectively be treated by cataract surgery, where the clouded lens is replaced by an artificial intraocular lens (IOL). Postoperative healing processes can cause a displacement of the IOL, which further leads to the fact that the quality of vision is deteriorated. Studies have shown that the imaging quality of high sophisticated IOL designs is more sensitive to lens displacements than simpler designs. The effects of IOL displacements are not well represented and tested within the current IOL test standard ISO 11979-2. This fact leads to the necessity to develope new test standards for novel and more sophisticated IOL designs. In this paper we present an improved model eye, which extends the current standard in three main aspects: First, the eye-model is very close to the physiology of the human eye. Second, electromechanic drives allow an automatic and precise simulation of postoperative lens tilts and decentrations, and finally in addition to standard conform MTF analysis, in the proposed setup also wavefront aberrations are measured. The latter reveals specific image aberrations caused by lens displacements. The model eye allows to objectively analyze the displacement tolerance of various IOL designs. The functionality of this novel setup is tested by measuring a spherical and an aspheric IOL design. Additionally, for comparison, IOLs that were already investigated with a previous version of the presented model eye are used for analysis. Measurements results reveal improvements compared to the previous version of the model eye and a functional prototype for wavefront measurement