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अमूर्त

Biomarkers Induced by the Immunomodulatory Bacterial Extract OM-85: Unique Roles for Peyer’s Patches and Intestinal Epithelial Cells

Vania Manolova, Anna Flace, Patricia Jeandet, Wolfgang C Bessler and Christian Pasquali

Objective: The orally administered bacterial lysate OM-85 (Broncho-Vaxom^®, Broncho-Munal^®, Ommunal^®, Paxoral^®, Vaxoral^®) is known to protect against recurrent respiratory tract infections. Despite mechanistic investigations performed during clinical and pre-clinical studies, little is known regarding the initial immune response to OM-85 following its passage through the stomach. To better understand the primary steps in the OM-85 gut-mediated immune-response cascade, we investigated its effects on two candidate cell types: intestinal epithelial cells (IECs) and Peyer’s patch (PP) leukocytes and confirmed its sustained immune effect in a reconstituted gastric buffer.
Methods: In order to confirm OM-85’s continued activity following gastric transit, THP-1 cells were stimulated with OM-85 following its incubation in reconstituted gastric buffer (pH 1.7, 8 pM Pepsin). The ability of OM-85 to stimulate IECs was tested by incubating epithelial-cell lines (Caco-2 and HT-29) and freshly isolated mouse IEC aggregates with OM-85 or standard pattern-recognition receptor (PRR) ligands (Pam₃CSK₄, LPS, flagellin, or PGN). To test the ability of OM-85 to stimulate mucosal immune cells, PP cells isolated from mouse intestine were incubated with OM-85 or PRR ligands.
Results: THP-1 cells released macrophage inflammatory protein-3 alpha (MIP-3α), both when OM-85 was pre-incubated in gastric buffer and when it was left untreated. In the presence of OM-85, functional PP cells freshly isolated from the intestine solely and dose-dependently released MIP-1α, a chemokine produced by myeloid cells which is involved in the recruitment and activation of various immune effector cells. Surprisingly, neither established epithelial-cell lines nor primary IECs of human or mouse origin released any of the tested cytokines in the presence of OM-85 or standard purified toll-like receptor (TLR)/nucleotide-binding oligomerisation domain (NOD)-like receptor ligands.
Conclusion: These data suggested that primary mucosal PPs, but not IECs, are activated by ligands from the bacterial lysate OM-85. The secretion of MIP-1α from PPs might be a trigger signal inducing tonic stimulation of mucosal tissues to prepare host immune defense towards invading pathogens.