Mechanism of TLR4-Mediated Anti-Inflammatory Response Induced by Exopolysaccharide from the Probiotic Bacillus subtilis.
Jesus Zamora-PinedaOlga KalininaAnne I SperlingKatherine L KnightPublished in: Journal of immunology (Baltimore, Md. : 1950) (2023)
Intestinal inflammatory diseases affect millions of people worldwide, and one class of drugs showing promise toward treatment of several inflammatory diseases is probiotics. Numerous studies have been performed using probiotics to prevent and treat intestinal inflammatory diseases. Most of these studies used intact bacteria, and neither the active molecule nor the molecular mechanisms by which they affect immune responses are known. We have shown that the probiotic Bacillus subtilis is anti-inflammatory and can protect mice from acute colitis induced by the enteric pathogen Citrobacter rodentium. We identified and purified the active molecule, exopolysaccharide (EPS), and showed that it protects mice from C. rodentium-induced colitis by inducing anti-inflammatory M2 macrophages or inhibitory dendritic cells (DCs), both of which inhibit excessive T cell responses. We showed previously that EPS affects macrophages and DCs in a TLR4-dependent manner, and in the current study we asked how EPS induces these anti-inflammatory cells and how they function to inhibit T cells. By investigating the signaling downstream of TLR4 that leads to acquisition of inhibitory properties of macrophages and DCs, we found that EPS induces expression of the inhibitory molecule IDO in bone marrow-derived DCs, and that inhibition of T cell proliferation by IDO-expressing bone marrow-derived DCs utilizes the kynurenine/aryl hydrocarbon receptor circuit. Furthermore, unlike LPS, EPS does not induce inflammatory cytokines upon injection in vivo, directly demonstrating different outcomes induced by two different TLR4 agonists.
Keyphrases
- anti inflammatory
- bacillus subtilis
- immune response
- toll like receptor
- dendritic cells
- inflammatory response
- cell proliferation
- oxidative stress
- induced apoptosis
- nuclear factor
- poor prognosis
- mesenchymal stem cells
- high fat diet induced
- liver failure
- type diabetes
- intensive care unit
- regulatory t cells
- cell cycle
- signaling pathway
- cell death
- weight gain
- candida albicans
- ulcerative colitis
- long non coding rna
- deep learning
- adipose tissue
- pi k akt
- aortic dissection