This might signify another contributing mechanism to host immune tolerance of MAP. Throughout the Intermediate Phase of MAP infection, larger amounts of perturbation of signaling and immune response associated pathways reflect active host pathogen interactions. Autocrine and paracrine cell cell signaling are very vital to the interaction and maintenance of homeostasis within the varied cell population from the intestinal mucosa. Host Immune Tolerance Non Responsive Immune Associated Pathways Pathways which might be non responsive could be an indicator of disrupted host processes by MAP. An exciting finding was that interaction of MAP with the host failed to induce several important immune relevant pathways all through all 3 phases of host response. These pathways integrated Fc Epsilon RI Signaling, B cell Receptor Signaling, Activation of CSK By T Cell Receptor Signaling, Pure Killer Cell Mediated Cytotox icity, and T Cell Receptor Signaling.
Fc epsilon RI signaling is exclusive to the mast cells. Suppression of mast cells activity thus have an effect on the innate responses of your host to release various activated molecules, such as biogenic amines, proteoglycans, lipid mediators this kind of selleck as leukotrienes, prostaglandins and secretion of cytokines, the most crucial of that are TNF a, IL4 and IL5. The suppression of these mediators, cytokines and T cell receptors signaling in addition to the up regulation within the epithelial fix mechanisms and reduced irritation may well improve MAP intracellular survival and facilitate persistent infection. BCR Signaling inactivity could imply that any signaling pathways emanating from your B cell antigens is likely not stimulating any B lymphocyte immune response. To more understand the mechanistic occasions which have been suppressing T cell activation, the CD40L Signaling and T cell Signaling pathways had been examined with the gene expression and network level.
Table 20 indicates the DBGGA gene Bayesian z score results throughout the Early, Intermediate and Late Phases of host immune response for CS pathway that shows a vast majority of critical genes as not substantially expressed. Suppression of genes while in the CS pathway could have a additional damaging regulation on a substantial number of genes implicated selleck chemicals in host defense towards pathogens. To the TCS pathway, the DBGGA evaluation clearly indicated a defective antigen processing and presentation by MHC class II molecule as shown in Figure 8a. On this graphical representation of T cell signaling, a few genes encoding MHC molecules weren’t differentially expressed. MAP infection did not change the expression level of co stimulatory molecules that are recognized to get involved within the activation of PI3K and GRB2 that ultimately activate NFkB. Interestingly, during MAP infection, LCK and NFATC1, NFATC4 are the mechanistic genes in T cell signaling pathway and activation of these genes leads to ubiquitin mediated proteolysis.