Bifidobacterium animalis in combination with human origin of Lactobacillus plantarum ameliorate neuroinflammation in experimental model of multiple sclerosis by altering CD4+ T cell subset balance

Autor: Reza Nosratabadi, Mahdieh Khazaee, Zohre Salehipour, Mahmoud Mahmoudi, Nafiseh Tabasi, Mojtaba Sankian, Leila Roozbeh Nasiraii, Mohammad Mehdi Soltan Dallal, Maryam Rastin, Dariush Haghmorad
Rok vydání: 2017
Předmět:
CD4-Positive T-Lymphocytes
0301 basic medicine
Encephalomyelitis
Autoimmune
Experimental
Multiple Sclerosis
medicine.medical_treatment
Population
Spleen
Nervous System
law.invention
03 medical and health sciences
Probiotic
0302 clinical medicine
Bifidobacterium animalis
Antigens
CD
law
medicine
Animals
Humans
RNA
Messenger
IL-2 receptor
education
Cell Proliferation
Inflammation
Pharmacology
education.field_of_study
biology
Probiotics
Experimental autoimmune encephalomyelitis
FOXP3
General Medicine
Immunotherapy
Th1 Cells
medicine.disease
biology.organism_classification
Lymphocyte Subsets
Mice
Inbred C57BL
Disease Models
Animal
030104 developmental biology
medicine.anatomical_structure
Spinal Cord
Immunology
Disease Progression
Cytokines
Th17 Cells
Female
Inflammation Mediators
030217 neurology & neurosurgery
Lactobacillus plantarum
Zdroj: Biomedicine & Pharmacotherapy. 95:1535-1548
ISSN: 0753-3322
Popis: Background Multiple Sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS). Recent reports have shown that probiotics can induce immunomodulatory activity with promising effects in inflammatory diseases. This study was designed to reveal the molecular and cellular mechanisms underlying the effect of Lactobacillus plantarum A7, which comprises human commensal bacteria, and Bifidobacterium animalis, a potential probiotic strain, on alleviation of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Methods To evaluate the therapeutic effects of probiotic strains, female C57BL/6 mice (8–10 wks old) received Lactobacillus plantarum A7, Bifidobacterium animalis PTCC 1631or a mixture of both strains through oral administration daily for 22 days beginning simultaneous with induction of EAE. The clinical parameters were recorded daily. On Day 22, each mouse was bled, and their spinal cord was removed for histology analysis. The effects of the treatments on regulatory T (Treg) cells level were evaluated using flow cytometry, and T-cell proliferation was assessed using a BrdU incorporation assay. The supernatants of spleen and lymph nodes cultured and mononuclear cells were collected for quantification of different panel of pro and anti-inflammatory cytokines by ELISA. The analysis of gene expression was performed at RNA level for transcription factors by real-time PCR. Results The results showed that treatment with a mixture of the two strains caused a more significant delay in the time of disease onset and clinical score compared to when the strains were used alone. The pathological features of the disease, such as mononuclear infiltration into the CNS, were also inhibited more significantly by the combinational approach. The results also revealed that treatment with combination of both strains enhanced the population of CD4+CD25+Foxp3+-expressing T-cells in the lymph nodes and the spleen. Treatment with our probiotic strains markedly inhibited disease associated cytokines while increased anti-inflammatory cytokines. Additionally, L. plantarumA7 and B. animalis ameliorated EAE condition by favoring Th2 and Treg differentiation via up-regulation of Foxp3 and GATA3 in the brain and spleen as well as inhibited the differentiation of Th1 and Th17 cells. Conclusions The current research provided evidence that probiotic therapy with L. plantarum and B. animalis can effectively attenuate EAE progression as well as reinforce the polarization of regulatory T-cells.
Databáze: OpenAIRE
Externí odkaz: