Neural Immune Communication in the Control of Host-Bacterial Pathogen Interactions in the Gastrointestinal Tract

The orchestration of host immune responses to enteric bacterial pathogens is a complex process involving the integration of numerous signals, including from the nervous system. Despite the recent progress in understanding the contribution of neuroimmune interactions in the regulation of inflammation, the mechanisms and effects of this communication during enteric bacterial infection are only beginning to be characterized. As part of this neuroimmune communication, neurons specialized to detect painful or otherwise noxious stimuli can respond to bacterial pathogens. Highlighting the complexity of these systems, the immunological consequences of sensory neuron activation can be either host adaptive or maladaptive, depending on the pathogen and organ system. These are but one of many types of neuroimmune circuits, with the vagus nerve and sympathetic innervation of numerous organs now known to modulate immune cell function and therefore dictate immunological outcomes during health and disease. Here, we review the evidence for neuroimmune communication in response to bacterial pathogens, and then discuss the consequences to host morbidity and mortality during infection of the gastrointestinal tract

CNF1 Increases Brain Energy Level, Counteracts Neuroinflammatory Markers and Rescues Cognitive Deficits in a Murine Model of Alzheimer's Disease

Overexpression of pro-inflammatory cytokines and cellular energy failure are associated with neuroinflammatory disorders, such as Alzheimer's disease. Transgenic mice homozygous for human ApoE4 gene, a well known AD and atherosclerosis animal model, show decreased levels of ATP, increased inflammatory cytokines level and accumulation of beta amyloid in the brain. All these findings are considered responsible for triggering cognitive decline. We have demonstrated that a single administration of the bacterial E. coli protein toxin CNF1 to aged apoE4 mice, beside inducing a strong amelioration of both spatial and emotional memory deficits, favored the cell energy restore through an increment of ATP content. This was accompanied by a modulation of cerebral Rho and Rac1 activity. Furthermore, CNF1 decreased the levels of beta amyloid accumulation and interleukin-1β expression in the hippocampus. Altogether, these data suggest that the pharmacological modulation of Rho GTPases by CNF1 can improve memory performances in an animal model of Alzheimer's disease via a control of neuroinflammation and a rescue of systemic energy homeostasis

Physiology and Pathophysiology of Venous Flow

International audienceVeins provide heart filling flow with lower velocity and pressure than those in arteries. The right heart receives systemic venous blood and pumps blood into the pulmonary circulation that returns oxygenated blood into the left heart for its ejection at high velocity and pressure into the systemic circulation.Whereas systemic veins carry deoxygenated blood from cells to the right cardiac pump, oxygenated blood flows in pulmonary veins running to the left cardiac pump, although pulmonary veins receive a part of the systemic venous blood that is drained from the lung tissue.Usually, one or two veins run with an artery, collecting lymphatic vessel, and nerve packaged in a sheath. In the head, veins follow paths that differ from those of arteries.Whereas venous flow in the standing position in veins below the heart level is supported by the hydrostatic pressure, blood flow in veins situated above this level must struggle against the gravity effect.Veins constitute the major blood storage compartment. They accommodate blood volume changes by dilating and shrinking to possibly reach a collapsed state. Veins, into which blood pressure is relatively small, are usually more deformable than accompanying arteries subjected to the same external pressure. However, deep veins embedded into skeletal muscle are less deformable than superficial veins close to the skin. Although both types for a given merging generation have similar wall thickness, they behave as thick- and thin-walled conduit, respectively. However, deep veins embedded into skeletal muscle are less deformable than superficial veins close to the skin. Although both types for a given merging generation have similar wall thickness, they behave as stiff and and soft conduit, respectively. In other words, deep and superficial veins can be represented by thin-walled veins in a gel and air, respectively, the former being mush less collapsible than the latter. Compression stocking (or supportive hose) diverts superficial venous flow of legs to deep veins that are less subjected to chronic venous insufficiency, as it collapses superficial veins without deforming deep veins.Similar to arterial flow, venous flow is unsteady, especially in abdominal and thoracic veins that experience both breathing and cardiac pumping. In addition, veins of the inferior and superior limbs undergo more or less transient external compression by contracting skeletal muscles. During walking, venous valves prevent backflow to the feet, whereas muscles ensure an additional pumping that favors venous return

Physiology and Pathophysiology of Arterial Flow

International audienceArterial flow is a three-dimensional unsteady process that is analyzed by measurements as well as physiological, biological, and mechanical experiments and numerical simulations. Few quantities can be noninvasively measured; they encompass cardiac frequency and peripheral arterial blood pressure as well as velocity and flow rate in given arterial stations by functional imaging. The central arterial blood pressure, from which clinicians derive several indices that are related to the physiological state of compartments of the cardiovascular apparatus, is measured using catheter-based transducers. Research is carried out to adequately infer the aortic pressure from measures in peripheral arteries using efficient signal processing.Blood flows through deformable arteries that dilate and constrict. The expansion of elastic arteries (Windkessel effect) that constitute the upstream compartment of the arterial tree transforms the systolic bolus into a pulsatile flow. Furthermore, the perfusion of the cardiac pump by coronary arteries benefits from the backflow generated by the wall recoil in elastic arteries. However, the arterial deformation is not only passive but also active. Mural cells sense and react to the stress field and adjust the caliber of the arterial lumen accordingly using intra-, auto-, juxta-, and paracrine signaling. The arterial wall is innervated and perfused from the lumen and vasa vasorum, hence receiving nervous and endocrine cues that are transduced for appropriate outputs. The vasomotor tone determines the level of the flow resistance.The regulation of the arterial flow has been widely investigated by physiologists, exhibiting the intricated and complex mechanisms that control the body’s homeostasis and adapt the local blood supply to the needs. At lower length scales, biologists describe the entire set of regulators and demonstrate their respective role and the functioning of signaling pathways in normal and pathological conditions. Biomechanicians develop new methods to assess the rheology and behavior of living tissues and, in collaboration with applied mathematicians, model physiological and pathophysiological processes. Some mechanical aspects that are easily handled in mechanics (e.g., applied to civil engineering and aeronautics) cannot be directly used in biomechanics. First, the architecture and the structure are much more complicated. Second, blood is carried in arterial lumens surrounded by three-layered walls made of composite materials. Both blood and wall are biological tissues, water being a major component. Hence, the fluid–structure interaction problem requires specific numerical treatment and elaboration of proper algorithms and multiphysics coupling softwares. Numerical tests are nevertheless carried out using simplifying assumptions and can be useful in medical practice

Purinergic receptors in the splanchnic circulation

There is considerable evidence that purines are vasoactive molecules involved in the regulation of blood flow. Adenosine is a well known vasodilator that also acts as a modulator of the response to other vasoactive substances. Adenosine exerts its effects by interacting with adenosine receptors. These are metabotropic G-protein coupled receptors and include four subtypes, A1, A2A, A2B and A3. Adenosine triphosphate (ATP) is a co-transmitter in vascular neuroeffector junctions and is known to activate two distinct types of P2 receptors, P2X (ionotropic) and P2Y (metabotropic). ATP can exert either vasoconstrictive or vasorelaxant effects, depending on the P2 receptor subtype involved. Splanchnic vascular beds are of particular interest, as they receive a large fraction of the cardiac output. This review focus on purinergic receptors role in the splanchnic vasomotor control. Here, we give an overview on the distribution and diversity of effects of purinergic receptors in splanchnic vessels. Pre- and post-junctional receptormediated responses are summarized. Attention is also given to the interactions between purinergic receptors and other receptors in the splanchnic circulation