Immunity against fungal beta 1,3 glucan carbohydrate in the gastrointestinal tract
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Inflammatory Bowel Disease (IBD) is a debilitating, life- long disease that affects about 1.4 millions Americans. Little is known about the pathogenesis of IBD and an effective cure still remains to be discovered. While there are numerous T cell targeting therapies for IBD, more research is still needed. Bispecific T Cell Engagers, BiTES, is a modified protein capable of engaging two antigens simultaneously; it is capable of activating T cells by circumventing the MHC protein molecule. This provides an alternative to the current molecular therapies for IBD. In addition to monoclonal therapy research, there has been a plethora of research on immunomodulatory molecules, such as β- glucan. The benefit of β-glucan has been shown with supplements and food sources alike in animal models. In this study, we used BiTES, CMPD-1, with an anti-CD3/ Dectin-1 epitopes capable of engaging T Cells and β-glucan in beads and fungi cell wall. CMPD-1 is capable of engaging Splenic and Lamina Propia T Cells from a C57BL/6 mice. Likewise, CMPD-1 engaged T cells to hyphae of C. albicans and A. fumigatus, which have a higher concentration of β-glucan than in the candida form. The data show a delayed in hyphae growth in yeast with CMPD-1 and a decrease in yeast growth for the first four hours when compared to non- BiTES molecules. Additionally, qualitative analysis of CMPD-1 shows a decrease A. fumigatus growth after a 72-hour incubation period. Splenic T cells from mice lacking Dectin-1 and Wild-type (WT) mouse strains where incubated with BiTES compound and yeast for 23 hours followed by a PrestoBlue killing assay to assess yeast cell viability. The PrestoBlue assay showed that CMPD-1 killed more A. fumigatus in both T cell subsets; although, the difference lacked statistical significance. The applications of this molecule as a therapeutic agent for IBD are promising, although, still in its infancy. An alternative use for this molecule is to train the immune system with the BiTES molecule in conjunction with β-glucan supplements to build immunity against opportunistic pathogens such as A. fumigatus and C. albicans that often cause havoc in IBD patients as a result of the changes in microbiota, and compromised integrity of the GI tract.