Extracellular vesicles (EVs) are nano-sized lipid-bilayer encapsulated vesicles produced by the cells. These EVs are released into the surrounding space by almost all cell types. The EVs help in intercellular communication via their payloads which contain various proteins, lipids, and nucleic acids generated from the donor cells and allow for synergistic responses in surrounding cells. In recent years, EVs have been increasingly important in treating infectious diseases, including respiratory tract infections, urinary tract infections, wound infections, sepsis, and intestinal infections. Studies have confirmed the therapeutic value of mesenchymal stem cell-derived EVs (MSC-EVs) for treating infectious diseases to eliminate the pathogen, modulate the resistance, and restore tissue damage in infectious diseases. This can be achieved by producing antimicrobial substances, inhibiting pathogen multiplication, and activating macrophage phagocytic activity. Pathogen compounds can be diffused by inserting them into EVs produced and secreted by host cells or by secreting them as microbial cells producing EVs carrying signalling molecules and DNA shielding infected pathogens from immune attack. EVs play a key role in infectious pathogenesis and hold great promise for developing innovative treatments. In this review, we discuss the role of MSC-EVs in treating various infectious diseases.
Salmonella enterica serovar typhimurium is the cause of significant morbidity and mortality worldwide that causes economic losses to poultry and is able to cause infection in humans. Indigenous chicken breeds are a potential source of animal protein and have the added advantage of being disease resistant. An indigenous chicken, Kashmir favorella and commercial broiler were selected for understanding the mechanism of disease resistance. Following infection in Kashmir favorella, three differentially expressed genes Nuclear Factor Kappa B (NF-κB1), Forkhead Box Protein O3 (FOXO3) and Paired box 5 (Pax5) were identified. FOXO3, a transcriptional activator, is the potential marker of host resistance in Salmonella infection. NF-κB1 is an inducible transcription factor which lays the foundation for studying gene network of the innate immune response of Salmonella infection in chicken. Pax5 is essential for differentiation of pre-B cells into mature B cell. The real time PCR analysis showed that in response to Salmonella Typhimurium infection a remarkable increase of NF-κB1 (P˂0.01), FOXO3 (P˂0.01) gene expression in liver and Pax5 (P˂0.01) gene expression in spleen of Kashmir favorella was observed. The protein–protein interaction (PPI) and protein-TF interaction network by STRINGDB analysis suggests that FOXO3 is a hub gene in the network and is closely related to Salmonella infection along with NF-κB1. All the three differentially expressed genes (NF-κB1, FOXO3 and PaX5) showed their influence on 12 interacting proteins and 16 TFs, where cyclic adenosine monophosphate Response Element Binding protein (CREBBP), erythroblast transformation-specific (ETSI), Tumour-protein 53(TP53I), IKKBK, lymphoid enhancer-binding factor-1 (LEF1), and interferon regulatory factor-4 (IRF4) play role in immune responses. This study shall pave the way for newer strategies for treatment and prevention of Salmonella infection and may help in increasing the innate disease resistance.
Potential single nucleotide polymorphisms (SNPs) were detected between two chicken breeds (Kashmir favorella and broiler) using deep RNA sequencing. This was carried out to comprehend the coding area alterations, which cause variances in the immunological response to Salmonella infection. In the present study, we identified high impact SNPs from both chicken breeds in order to delineate different pathways that mediate disease resistant/susceptibility traits. Samples (liver and spleen) were collected from Salmonella resistant (K. favorella) and susceptible (broiler) chicken breeds. Salmonella resistance and susceptibility were checked by different pathological parameters post infection. To explore possible polymorphisms in genes linked with disease resistance, SNP identification analysis was performed utilizing RNA seq data from nine K. favorella and ten broiler chickens. A total of 1778 (1070 SNPs and 708 INDELs) and 1459 (859 SNPs and 600 INDELs) were found to be specific to K. favorella and broiler, respectively. Based on our results, we conclude that in broiler chickens the enriched pathways mostly included metabolic pathways like fatty acid metabolism, carbon metabolism and amino acid metabolism (Arginine and proline metabolism), while as in K. favorella genes with high impact SNPs were enriched in most of the immune-related pathways like MAPK signaling pathway, Wnt signaling pathway, NOD-like receptor signaling pathway, etc., which could be a possible resistance mechanism against salmonella infection. In K. favorella, protein–protein interaction analysis also shows some important hub nodes, which are important in providing defense against different infectious diseases. Phylogenomic analysis revealed that indigenous poultry breeds (resistant) are clearly separated from commercial breeds (susceptible). These findings will offer fresh perspectives on the genetic diversity in chicken breeds and will aid in the genomic selection of poultry birds.
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