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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
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
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.