Transient skin stretching stimulates immune surveillance and promotes vaccine delivery via hair follicles

Upon tissue injury, skin mechano-sensing promotes immune defense and return to homeostasis. However, the impact of acute skin stretching, such as skin rubbing, is poorly understood. Using a model of transient skin stretching, we show that a single instance of skin tension modification induces collagen fiber re-orientation, mechano-transduction in stromal cells, inflammatory mediator production, and immune cell recruitment to the skin. At the same time, skin stretching increases skin permeability without tissue damage via the opening of hair follicles. Furthermore, stretch-induced skin changes lead to the activation and migration of dermal dendritic cells through exposure to skin microbiota-derived compounds. Finally, we harness acute skin stretching to enable needle-free vaccine delivery, promoting antigen accumulation in the lymph nodes and producing a superior response compared to intramuscular injection. Our results shed light on the role of mechanical stimuli in fine-tuning skin immune surveillance and have important implications for drug delivery and mechanobiology.</p

Profiling of Differentially Expressed Genes Using Suppression Subtractive Hybridization in an Equine Model of Chronic Asthma

Background :\ud Gene expression analyses are used to investigate signaling pathways involved in diseases. In asthma, they have been primarily derived from the analysis of bronchial biopsies harvested from mild to moderate asthmatic subjects and controls. Due to ethical considerations, there is currently limited information on the transcriptome profile of the peripheral lung tissues in asthma.\ud \ud Objective :\ud To identify genes contributing to chronic inflammation and remodeling in the peripheral lung tissue of horses with heaves, a naturally occurring asthma-like condition.\ud \ud Methods :\ud Eleven adult horses (6 heaves-affected and 5 controls) were studied while horses with heaves were in clinical remission (Pasture), and during disease exacerbation induced by a 30-day natural antigen challenge during stabling (Challenge). Large peripheral lung biopsies were obtained by thoracoscopy at both time points. Using suppression subtractive hybridization (SSH), lung cDNAs of controls (Pasture and Challenge) and asymptomatic heaves-affected horses (Pasture) were subtracted from cDNAs of horses with heaves in clinical exacerbation (Challenge). The differential expression of selected genes of interest was confirmed using quantitative PCR assay.\ud \ud Results :\ud Horses with heaves, but not controls, developed airway obstruction when challenged. Nine hundred and fifty cDNA clones isolated from the subtracted library were screened by dot blot array and 224 of those showing the most marked expression differences were sequenced. The gene expression pattern was confirmed by quantitative PCR in 15 of 22 selected genes. Novel genes and genes with an already defined function in asthma were identified in the subtracted cDNA library. Genes of particular interest associated with asthmatic airway inflammation and remodeling included those related to PPP3CB/NFAT, RhoA, and LTB4/GPR44 signaling pathways.\ud \ud Conclusions :\ud Pathways representing new possible targets for anti-inflammatory and anti-remodeling therapies for asthma were identified. The findings of genes previously associated with asthma validate this equine model for gene expression studies

PREVALENCE DE LA COQUELUCHE CHEZ L'ADULTE PRESENTANT UNE TOUX PERSISTANTE ET CONSULTANT EN MEDECINE GENERALE

PARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF

Species-Level Gut Microbiota Analysis after Antibiotic-Induced Dysbiosis in Horses

All current studies have used Illumina short-read sequencing to characterize the equine intestinal microbiota. Long-read sequencing can classify bacteria at the species level. The objectives of this study were to characterize the gut microbiota of horses at the species level before and after trimethoprim sulfadiazine (TMS) administration and to compare results with Illumina sequencing. Nine horses received TMS (30 mg/kg) orally for 5 days twice a day to induce dysbiosis. Illumina sequencing of the V4 region or full-length PacBio sequencing of the 16S rRNA gene was performed in fecal samples collected before and after antibiotic administration. The relative abundance and alpha diversity were compared between the two technologies. PacBio failed to classify the equine intestinal microbiota at the species level but confirmed Bacteroidetes as the most abundant bacteria in the feces of the studied horses, followed by Firmicutes and Fibrobacteres. An unknown species of the Bacteroidales order was highly abundant (13%) and deserves further investigation. In conclusion, PacBio was not suitable to classify the equine microbiota species but detected greater richness and less unclassified bacteria. Further efforts in improving current databanks to be used in equine studies are necessary

Species-Level Gut Microbiota Analysis after Antibiotic-Induced Dysbiosis in Horses

All current studies have used Illumina short-read sequencing to characterize the equine intestinal microbiota. Long-read sequencing can classify bacteria at the species level. The objectives of this study were to characterize the gut microbiota of horses at the species level before and after trimethoprim sulfadiazine (TMS) administration and to compare results with Illumina sequencing. Nine horses received TMS (30 mg/kg) orally for 5 days twice a day to induce dysbiosis. Illumina sequencing of the V4 region or full-length PacBio sequencing of the 16S rRNA gene was performed in fecal samples collected before and after antibiotic administration. The relative abundance and alpha diversity were compared between the two technologies. PacBio failed to classify the equine intestinal microbiota at the species level but confirmed Bacteroidetes as the most abundant bacteria in the feces of the studied horses, followed by Firmicutes and Fibrobacteres. An unknown species of the Bacteroidales order was highly abundant (13%) and deserves further investigation. In conclusion, PacBio was not suitable to classify the equine microbiota species but detected greater richness and less unclassified bacteria. Further efforts in improving current databanks to be used in equine studies are necessary.</jats:p

Effects of magnesium sulfate infusion on clinical signs and lung function of horses with severe asthma

Abstract OBJECTIVE To evaluate whether MgSO4 solution administered IV would improve the clinical signs and lung function of horses with severe asthma and potentiate the effects of salbutamol inhalation in those horses. ANIMALS 6 adult horses with severe asthma. PROCEDURES Asthmatic horses were used in 3 crossover design experiments (6 treatments/horse). Clinical scores for nasal flaring and the abdominal component associated with breathing and lung function were determined before and after administration of salbutamol (800 μg, by inhalation), MgSO4 solution (2.2 mg/kg/min, IV, over 20 minutes), and combined MgSO4-salbutamol treatment. The data were collected during experimental procedures to assess salbutamol inhalation versus mock inhalation, MgSO4 infusion versus infusion of saline (NaCl) solution (adjusted to the same osmolarity as the MgSO4 solution), and the combined MgSO4-salbutamol treatment versus salbutamol inhalation alone. RESULTS Infusion of MgSO4 significantly improved clinical scores when administered alone or in combination with salbutamol inhalation. With the combination treatment, lung function improved, albeit not significantly. Tidal volume also increased following combined MgSO4-salbutamol treatment. Salbutamol alone significantly improved lung function, whereas saline solution administration and a mock inhalation procedure had no effect on the studied variables. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that MgSO4 infusion alone or in combination with salbutamol inhalation improved the clinical signs of severely asthmatic horses. The effects of MgSO4 were not associated with significant lung function improvement, which suggested that the changes observed were attributable to alterations in the horses' breathing patterns. Infusion of MgSO4 solution at the studied dose offers little advantage over currently used medications for the treatment of severe equine asthma.</jats:p