Porphyromonas gingivalis and Lactobacillus rhamnosus GG regulate the Th17/Treg balance in colitis via TLR4 and TLR2.
Clin Transl Immunology
; 9(11): e1213, 2020.
Article
em En
| MEDLINE
| ID: mdl-33282294
ABSTRACT
OBJECTIVES:
CD4+ T cells are the key to many immune-inflammatory diseases mediated by microbial disorders, especially inflammatory bowel disease (IBD). The purpose of this study was to explore how pathogenic and probiotic bacteria directly affect the T helper (Th)17 and T regulatory (Treg) cell balance among CD4+ T cells to regulate inflammation.METHODS:
Porphyromonas gingivalis (Pg; ATCC 33277) and Lactobacillus rhamnosus GG (LGG; CICC 6141) were selected as representative pathogenic and probiotic bacteria, respectively. Bacterial extracts were obtained via ultrasonication and ultracentrifugation. Flow cytometry, RT-qPCR, ELISAs, immunofluorescence and a Quantibody cytokine array were used. The dextran sodium sulphate (DSS)-induced colitis model was selected for verification.RESULTS:
The Pg ultrasonicate induced the apoptosis of CD4+ T cells and upregulated the expression of the Th17-associated transcription factor RoRγt and the production of the proinflammatory cytokines IL-17 and IL-6, but downregulated the expression of the essential Treg transcription factor Foxp3 and the production of the anti-inflammatory factors TGF-ß and IL-10 via the TLR4 pathway. However, LGG extract maintained Th17/Treg homeostasis by decreasing the IL-17+ Th17 proportion and increasing the CD25+ Foxp3+ Treg proportion via the TLR2 pathway. In vivo, Pg-stimulated CD4+ T cells aggravated DSS-induced colitis by increasing the Th17/Treg ratio in the colon and lamina propria lymphocytes (LPLs), and Pg + LGG-stimulated CD4+ T cells relieved colitis by decreasing the Th17/Treg ratio via the JAK-STAT signalling pathway.CONCLUSIONS:
Our findings suggest that pathogenic Pg and probiotic LGG can directly regulate the Th17/Treg balance via different TLRs.
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MEDLINE
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article