Exopolysaccharide from Bifidobacterium longum subsp. longum 35624™ modulates murine allergic airway responses

Abstract

Interactions between the host and the microbiota are thought to significantly influence immunological tolerance mechanisms at mucosal sites. We recently described that the loss of an exopolysaccharide (EPS) from Bifidobacterium longum 35624™ eliminated its protective effects in colitis and respiratory allergy murine models. Our goal was to investigate the immune response to purified EPS from B. longum 35624, determine if it has protective effects within the lung and identify the protective mechanisms. Isolated EPS from B. longum 35624 cultures was used for in vitro, ex vivo and in vivo studies. Human monocyte-derived dendritic cells (MDDCs) were used to investigate in vitro immunological responses to EPS. Cytokine secretion, expression of surface markers and signalling pathways were examined. The ovalbumin (OVA) respiratory allergy murine model was used to evaluate the in vivo immunomodulatory potential of EPS. In addition, interleukin (IL)-10 knockout (KO) mice and anti-Toll-like receptor (TLR)-2 blocking antibody were used to examine the underlying protective mechanisms of intranasal EPS administration. Stimulation of human MDDCs with EPS resulted in IL-10 secretion, but not proinflammatory cytokines. IL-10 secretion was TLR-2-dependent. Eosinophil recruitment to the lungs was significantly decreased by EPS intranasal exposure, which was associated with decreased expression of the Th2-associated markers C-C motif chemokine 11 (CCL11), C-C chemokine receptor type 3 (CCR3), IL-4 and IL-13. TLR-2-mediated IL-10 secretion was shown to be required for the reduction in eosinophils and Th2 cytokines. EPS-treatment reduced eosinophil recruitment within the lung in a respiratory inflammation mouse model, which is both TLR-2 and IL-10 mediated. EPS can be considered as a novel molecule potentially reducing the severity of chronic eosinophil-related airway disorders.

Precision medicine and phenotypes, endotypes, genotypes, regiotypes, and theratypes of allergic diseases

“…Particular gut commensals, such as Bifidobacterium longum, are known to show protection from inflammatory diseases. Recently, a molecular mechanism of action was ascribed to exopolysaccharide produced by the commensal bacteria (116,117).…”

Airway Microbiome in Different Inflammatory Phenotypes of Asthma: A Cross-Sectional Study in Northeast China

“…Bifidobacterium , has been observed with a lower level in the airway of EA in present study. This genus could suppress the Th2 type immune response within the lungs of allergic asthma and reduce the recruitment of eosinophil into the lungs by producing exopolysaccharide 30, a high-molecular compound with various potent immunomodulatory activities 31, 32. Therefore, the differential level of Bifidobacterium may contribute to the formation of inflammatory phenotypes.…”

Bifidobacterial Dialogue With Its Human Host and Consequent Modulation of the Immune System

“…Moreover, the intranasal administration of EPS-producing B. longum 35624 and the EPS neg strains to ovalbumin respiratory allergy model mice, resulted in enhanced recruitment of IL-17 + lymphocytes to the murine lung. In this context, a further study showed the capability of B. longum 35624 EPS to suppress the Th2 type immune response within the lungs of ovalbumin sensitized mice when they were intranasally treated with purified B. longum 35624 EPS (57). All together these observations emphasize that the EPS of B. longum 35624 plays an important role in reducing the proinflammatory response.…”