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1.
J Immunotoxicol ; 17(1): 10-20, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-31909636

RESUMO

Mucosal-associated invariant T-cells (MAIT) can react to metabolites of the vitamins riboflavin and folate which are produced by the human gut microbiota. Since several studies showed that the pesticide chlorpyrifos (CPF) and glyphosate (GLP) can impair the gut microbiota, the present study was undertaken to investigate the impact of CPF and GLP treatment on the metabolism of gut microbiota and the resulting bacteria-mediated modulation of MAIT cell activity. Here, Bifidobacterium adolescentis (B. adolescentis), Lactobacillus reuteri (L. reuteri), and Escherichia coli (E. coli) were treated with CPF (50-200 µM) or GLP (75-300 mg/L) and then used in MAIT cell stimulation assays as well as in vitamin and proteome analyses. All three bacteria were nonpathogenic and chosen as representatives of a healthy human gut microflora. The results showed that E. coli activated MAIT cells whereas B. adolescentis and L. reuteri inhibited MAIT cell activation. CPF treatment significantly increased E. coli-mediated MAIT cell activation. Treatment of B. adolescentis and L. reuteri with CPF and GLP weakened the inhibition of MAIT cell activation. Riboflavin and folate production by the test bacteria was influenced by CPF treatment, whereas GLP had only minor effects. Proteomic analysis of CPF-treated E. coli revealed changes in the riboflavin and folate biosynthesis pathways. The findings here suggest that the metabolism of the analyzed bacteria could be altered by exposure to CPF and GLP, leading to an increased pro-inflammatory immune response.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Herbicidas/toxicidade , Inseticidas/toxicidade , Ativação Linfocitária/efeitos dos fármacos , Células T Invariantes Associadas à Mucosa/imunologia , Bifidobacterium adolescentis/efeitos dos fármacos , Bifidobacterium adolescentis/imunologia , Bifidobacterium adolescentis/metabolismo , Vias Biossintéticas/efeitos dos fármacos , Vias Biossintéticas/imunologia , Buffy Coat/citologia , Clorpirifos/toxicidade , Escherichia coli/efeitos dos fármacos , Escherichia coli/imunologia , Escherichia coli/metabolismo , Ácido Fólico/análise , Ácido Fólico/biossíntese , Microbioma Gastrointestinal/imunologia , Glicina/análogos & derivados , Glicina/toxicidade , Voluntários Saudáveis , Interações entre Hospedeiro e Microrganismos/efeitos dos fármacos , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Limosilactobacillus reuteri/efeitos dos fármacos , Limosilactobacillus reuteri/imunologia , Limosilactobacillus reuteri/metabolismo , Ativação Linfocitária/imunologia , Proteômica , Riboflavina/análise , Riboflavina/biossíntese , Glifosato
2.
Nutrients ; 11(4)2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30987344

RESUMO

Intestinal bifidobacteria benefit human health by promoting and modulating the gut flora, and boosting therapeutic efficiency for chronic metabolic diseases and cancer. Recently, Bifidobacterium adolescentis strains with high adhesion to intestinal epithelial cells were associated with induction of T-helper 17 (Th17) cells in humans and rodents. Here, two B. adolescentis strains with similar adhesive ability but different aggregation properties were investigated for specific immunoregulatory effects, including the underlying cellular pathway, on macrophage and T-regulatory (Treg)/Th17 axis activation in vitro and in the colon of dextran sodium sulfate (DSS)-colitis mice in vivo. In-vitro, the auto-aggregative B. adolescentis strain IF1-11 induced significantly higher IL-6 and lower IL-10 secretion from immune cells, and it induced abundant Th17 cells. The non-aggregating strain IF1-03 induced significantly higher IL-10, less IL-6 and a high proportion of Treg/Th17 cells compared to total T cells. In vivo, orally administered IF1-03 protected DSS-colitis mice via activation of dendritic cells or macrophages and skewing of Treg/Th17 cells, consistent with Treg cell induction in vitro. IF1-03 exopolysaccharides showed a functional recognition pattern similar to IF1-03 for IL-10 cytokine secretion and Treg cell-differentiation induction, both dependent on the toll-like receptor 2-ERK/p38 MAPK-signaling cascade for macrophage activation. We suggest that B. adolescentis exopolysaccharide-associated enterocyte adhesion/aggregation phenotypes determine strain-specific adaptive immune responses in the gut via the macrophage-regulated Treg/Th17 axis.


Assuntos
Aderência Bacteriana , Bifidobacterium adolescentis/metabolismo , Colite/prevenção & controle , Colo/microbiologia , Microbioma Gastrointestinal , Polissacarídeos Bacterianos/metabolismo , Probióticos/administração & dosagem , Linfócitos T Reguladores/microbiologia , Células Th17/microbiologia , Animais , Bifidobacterium adolescentis/imunologia , Colite/imunologia , Colite/metabolismo , Colite/microbiologia , Colo/imunologia , Colo/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Células Dendríticas/microbiologia , Sulfato de Dextrana , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Interações Hospedeiro-Patógeno , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Polissacarídeos Bacterianos/imunologia , Células RAW 264.7 , Transdução de Sinais , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Células Th17/imunologia , Células Th17/metabolismo , Receptor 2 Toll-Like/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
3.
Proc Natl Acad Sci U S A ; 113(50): E8141-E8150, 2016 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-27911839

RESUMO

Th17 cells accrue in the intestine in response to particular microbes. In rodents, segmented filamentous bacteria (SFB) induce intestinal Th17 cells, but analogously functioning microbes in humans remain undefined. Here, we identified human symbiont bacterial species, in particular Bifidobacterium adolescentis, that could, alone, induce Th17 cells in the murine intestine. Similar to SFB, B. adolescentis was closely associated with the gut epithelium and engendered cognate Th17 cells without attendant inflammation. However, B. adolescentis elicited a transcriptional program clearly distinct from that of SFB, suggesting an alternative mechanism of promoting Th17 cell accumulation. Inoculation of mice with B. adolescentis exacerbated autoimmune arthritis in the K/BxN mouse model. Several off-the-shelf probiotic preparations that include Bifidobacterium strains also drove intestinal Th17 cell accumulation.


Assuntos
Bifidobacterium adolescentis/imunologia , Microbioma Gastrointestinal/imunologia , Mucosa Intestinal/citologia , Mucosa Intestinal/microbiologia , Células Th17/imunologia , Animais , Artrite Experimental/etiologia , Artrite Experimental/imunologia , Artrite Experimental/microbiologia , Bifidobacterium adolescentis/isolamento & purificação , Feminino , Perfilação da Expressão Gênica , Vida Livre de Germes/genética , Vida Livre de Germes/imunologia , Humanos , Imunidade nas Mucosas , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/patologia , Mucosa Intestinal/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Probióticos , Simbiose/genética , Simbiose/imunologia , Células Th17/citologia
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