Abstract
Th17-mediated mucosal inflammation is related to increased Prevotella bacterial abundance. The actual involvement of Prevotella in the development and accumulation of intestinal Th17 cells at a steady state, however, remains undefined. Herein, we investigated the role of Prevotella in inducing intestinal Th17 cells in mice. Mice were treated with a combination of broad-spectrum antibiotics (including ampicillin, neomycin sulfate, vancomycin hydrochloride, and metronidazole) in their drinking water for 4 weeks and then gavaged with Prevotella for 4 weeks. After inoculation, 16S rDNA sequencing was used to verify the colonization of Prevotella in the colon of mice. The IL-17A as well as IL-17A-expressing T cells was localized and quantified by an immunofluorescence assay (IFA) of colon sections. Th17 cells in the mesenteric lymph nodes of mice were counted by flow cytometry. Systemic immune response to Prevotella colonization was evaluated based on the serum levels of IL-6, TNF-α, IL-1β, IL-17A, IL-10, IL-4, IFN-γ, and IL-2. Th17-polarizing cytokines (IL-6, TNF-α, IL-1β, and IL-2) induced by Prevotella were evaluated by stimulation of bone marrow-derived dendritic cells (BMDCs). Results revealed that after inoculation, Prevotella successfully colonized the intestine of mice and induced the production and accumulation of colonic Th17 cells in the colon. Moreover, Prevotella elevated some of the Th17-related cytokines in the serum of mice. And Th17-polarizing cytokines (IL-6 and IL-1β) produced by BMDCs were mediated mainly through the interaction between Prevotella and Toll-like receptor 2 (TLR2). In conclusion, our data suggest that Prevotella induces the production of Th17 cells in the colon of mice, thus highlighting the potential role of Prevotella in training the intestinal immune system.
Highlights
The central role of the microbiota in human disease and health is gaining more attention since it can shape host immune development and modulate host immune responses [1]
Mice were treated with ABX for 4 weeks to deplete commensal organisms in the gut and gavaged with P. melaninogenica (WT+PM), P. copri (WT+PC), or blank medium (WT+BM) every other day for 4 weeks (Figure 1(a))
For the induction of IL-12, there was no significant difference between the two species of Prevotella, compared with PBS, P. copri showed statistical difference while P. melaninogenica did not (Figure 6(d)). These findings suggest that Prevotella can induce bone marrow-derived dendritic cells (BMDCs) to produce innate cytokines (i.e., TNF-α and IL-1β) and Th17- (i.e., IL-6 and IL-1β) and Th1- (i.e., IL-12) related cytokines
Summary
The central role of the microbiota in human disease and health is gaining more attention since it can shape host immune development and modulate host immune responses [1]. Certain bacterial species from Bacteroides and Clostridium have been identified to induce regulatory T cells in the murine colon [2,3,4,5]. Another study showed that a subgroup of microbes in the intestine, such as segmented filamentous bacteria (SFB), Citrobacter rodentium, and Escherichia coli O157, can induce the production of Th17 cells in the intestine [6]. There is epidemiological evidence for the relationship between Prevotella and increased Th17-mediated immune responses in many inflammatory diseases [14,15,16]
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