The immunomodulatory role of lipoteichoic acid from probiotic bacteria : a thesis presented in partial fulfilment of the requirements for the degree of Master of Science in Biochemistry, Institute of Molecular BioSciences, Massey University, Palmerston North, New Zealand

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Different probiotics provide different health benefits, and some of these may be explained by immunomodulatory activity. These immunomodulatory effects can vary between different probiotic strains and microbial-associated molecular patterns (MAMPs) may be responsible for this variation. One MAMP, lipoteichoic acid (LTA), is a macroamphiphile associated with the cell surface of gram positive bacteria. LTAs from different strains of bacteria have been shown to induce different immunomodulatory profiles. LTA was purified from three strains of lactic acid bacteria (LAB) that are known to elicit different immune responses, then analysed for immunomodulatory activity using human cell based assays. The activity of each LTA was shown to reflect elements of the immunomodulatory profile of the original strain. The structure of each LTA was determined using NMR (nuclear magnetic resonance spectroscopy). Structural differences found between the LTAs were compared to the differences in their immunomodulatory behaviours, showing that the differing structures may be responsible for strain-specific immune profiles. It has been previously shown that inactivation of the dltD gene in an established probiotic strain of LAB results in changes to the immune effects induced by the mutant bacterial cell compared to the wild type. This study has shown using NMR analysis that the structure of LTA isolated from this mutant strain is altered, reflecting the distinct immune profile of the mutant bacteria. LTAs from the three strains in this study were found to contain N-acetyl-glucosamine substituents, which have previously been found only on highly pro-inflammatory LTAs, e.g., those from Staphylococcus aureus. LTAs from the three strains were also shown to contain unsaturated fatty acids, which have so far been found in the LTAs of only LAB, including three other probiotic strains. These structural features may explain some of the immunomodulatory effects observed for these strains. It was found that isolated LTA may not be as effective at inducing immune responses as LTA on cells. Further exploration of potential interactions of LTA with other MAMPs, and other factors that may alter the presentation of LTA to immune cells in the case of intact cells is necessary to fully understand the role of LTA in immunomodulation.
Probiotics, Immune response, Lipoteichoic acid, Gram-positive bacteria