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

Particle size distribution of limestone fillers: granulometry and specific surface area investigations

Mineral fillers can be defined as “inert materials included in a mix design for some useful purpose”. They can be added to compounds in order to complete a large variety of final properties without increasing costs or to improve specific characteristics like hardness, brittleness, impact strength, compressive strength, softening point, fire resistance, surface texture, electrical conductivity, …etc. In Belgium, locally available limestone fillers are specifically very well-adapted for the optimisation of particle packing and flow behaviour of cementitious pastes in concrete mixes. Limestone fillers may be easily characterized in terms of chemical and mineralogical properties. These properties are fundamental for the study of the behaviour of concrete mixes in fresh state and for understanding interactions existing at the level of the Interfacial Transition Zone between aggregates and cement paste. These properties are however insufficiently discriminant and particle size, as well as shape distribution, seem to have a potential influence on physical phenomena which happen during the setting process. The aim of this paper is to compare five major techniques used to quantify the size and the shape of limestone fillers particles: laser diffraction scattering, wet sieving and image analysis for particle size measurement and BET adsorption and Blaine permeability methods for specific surface area