Figure 8.

Proposed Mechanism of How Weakly Agonistic LPSBV Influences MD-2/TLR4 Receptor Complex Activation and Prevents the Initiation of a CD4⁺ T Cell-Mediated Immune Response via Modulation of the Intestinal CD11c⁺ Cells

Therapeutic administration of LPS from symbiotic B. vulgatus mpk ends up in large amounts in the intestine, exceeding the amount of present LPS from other intestinal commensal bacteria. Excess LPSBV primes naive CD11c⁺ cells into a tolerant, tolerogenic, and semi-mature phenotype that fails to activate CD4⁺ T cells. This prevention of a de novo activation of CD4⁺ T cells leads to a phase-out of ongoing inflammatory processes, while de novo induction of an immune response is prevented. However, our data indicate that this only happens if LPSBV is the only TLR4 ligand that CD11c⁺ cells encounter when they are still naive and immature. LPSBV needs a certain period of time to induce CD11c⁺ cell tolerance. Simultaneous encounter with agonistic LPS does not lead to CD11c⁺ cell tolerance, and it does not, therefore, promote abrogation of inflammatory processes.