Three in a Box: Understanding Cardiomyocyte, Fibroblast, and Innate Immune Cell Interactions to Orchestrate Cardiac Repair Processes

Following an insult by both intrinsic and extrinsic pathways, complex cellular, and molecular interactions determine a successful recovery or inadequate repair of damaged tissue. The efficiency of this process is particularly important in the heart, an organ characterized by very limited regenerative and repair capacity in higher adult vertebrates. Cardiac insult is characteristically associated with fibrosis and heart failure, as a result of cardiomyocyte death, myocardial degeneration, and adverse remodeling. Recent evidence implies that resident non-cardiomyocytes, fibroblasts but also macrophages -pillars of the innate immunity- form part of the inflammatory response and decisively affect the repair process following a cardiac insult. Multiple studies in model organisms (mouse, zebrafish) of various developmental stages (adult and neonatal) combined with genetically engineered cell plasticity and differentiation intervention protocols -mainly targeting cardiac fibroblasts or progenitor cells-reveal particular roles of resident and recruited innate immune cells and their secretome in the coordination of cardiac repair. The interplay of innate immune cells with cardiac fibroblasts and cardiomyocytes is emerging as a crucial platform to help our understanding and, importantly, to allow the development of effective interventions sufficient to minimize cardiac damage and dysfunction after injury

The role of respiratory viruses in the origin and exacerbations of asthma

Purpose of review The present review focuses and comments on the increasing body of evidence correlating respiratory viral infections with asthma onset and exacerbations. Recent findings Recent data suggest multiple and some time contrasting roles for viral infection in the origin of asthma. These data also indicate that the immune status of the host, including atopy, may interactively contribute to this process, conferring susceptibility or even resistance to the development of asthma in virus-infected individuals. In the presence of asthma, the role of viral infection in triggering exacerbations is clearly established. Chemokine and cytokine responses of the respiratory epithelium, a biased type 1/type 2 cytokine balance, defective costimulation, as well as abnormal neural control have been suggested as possible mechanisms. The importance of concurrent or synergistic effects of allergen exposure is currently under scrutiny. Summary Viruses may initiate and certainly exacerbate asthma. Mild repeated infections early in life could also stimulate type 1 immune responses conferring protection from atopy and asthma. The host’s immune status, the type of viral infection and the timing of exposure to various environmental stimuli are probably the key factors in this process. Mechanistic insights deduced from recent work should allow for the development of intervening strategies in the near future

Does respiratory syncytial virus subtype influences the severity of acute bronchiolitis in hospitalized infants?

AbstractRespiratory syncytial virus (RSV) subtypes A and B are present either simultaneously or alternate during yearly epidemics. It is still not clear whether clinical severity of acute bronchiolitis differs between the two subtypes.Reverse transcription polymerase chain reaction was used to subtype RSV in previously healthy infants hospitalized with RSV bronchiolitis during a winter epidemic. A severity index based on heart rate, respiratory rate, wheezing, difficulty in feeding and oxygen saturation was calculated upon admission.Infants infected with RSV subtype-A were found to have a significantly higher (more severe) clinical score than those infected with RSV-B. There was no statistically significant difference in duration of hospitalization or need of intensive care. Boys and infants younger than 3 months of age were also more severely affected than girls or older infants, respectively.These results support the notion that RSV-A-induced bronchiolitis is more severe than RSV-B-induced one, in agreement with the majority of previously published studies

Homoclinic bifurcations and uniform hyperbolicity for three-dimensional flows

In inflammatory bowel disease (IBD), compromised restitution of the epithelial barrier contributes to disease severity. Owing to the complexity in the pathogenesis of IBD, a variety of factors have been implicated in its progress. In this study, we report a functional interaction between macroautophagy and Corticotropin Releasing Hormone (Crh) in the gut. For this purpose we used DSS colitis model on Crh ?/? or wild-type (wt) with pharmacological inhibition of autophagy. We uncovered sustained basal autophagy in the gut of Crh ?/? mice, which persisted over the course of DSS administration. Autophagy inhibition resulted in partial rescue of Crh ?/? mice, while it increased the expression of Crh in the wt gut. Similarly, Crh deficiency was associated with sustained activation of base line autophagy. In vitro models of amino acid deprivation- and LPS-induced autophagy confirmed the in vivo findings. Our results indicate a novel role for Crh in the intestinal epithelium that involves regulation of autophagy, while suggesting the complementary action of the two pathways. These data suggest the intriguing possibility that targeting Crh stimulation in the intestine may provide a novel therapeutic approach to support the integrity of the epithelial barrier and to protect from chronic colitis