The microbiota is a crucial modulator of the immune system. Here, we evaluated how its absence or reduction modifies the inflammatory response in the murine model of experimental autoimmune uveoretinitis (EAU). We induced EAU in germ-free (GF) or conventionally housed (CV) mice and in CV mice treated with a combination of broad-spectrum antibiotics either from the day of EAU induction or from one week prior to induction of disease. The severity of the inflammation was assessed by fundus biomicroscopy or by histology, including immunohistology. The immunophenotyping of T cells in local and distant lymph nodes was performed by flow cytometry. We found that GF mice and mice where the microbiota was reduced one week before EAU induction were protected from severe autoimmune inflammation. GF mice had lower numbers of infiltrating macrophages and significantly less T cell infiltration in the retina than CV mice with EAU. GF mice also had reduced numbers of IFN-γ and IL-17-producing T cells and increased numbers of regulatory T cells in the eye-draining lymph nodes. These data suggest that the presence of microbiota during autoantigen recognition regulates the inflammatory response by influencing the adaptive immune response.

• MeSH
• adaptivní imunita MeSH
• aktivace lymfocytů MeSH
• antibakteriální látky farmakologie   MeSH
• autoantigeny imunologie   MeSH
• autoimunitní nemoci chemicky indukované   imunologie   mikrobiologie   MeSH
• bakteriální nálož účinky léků   MeSH
• gnotobiologické modely MeSH
• interferon gama biosyntéza   MeSH
• interleukin-17 biosyntéza   MeSH
• makrofágy imunologie   MeSH
• mikrobiota * imunologie   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• oči imunologie   patologie   MeSH
• oční proteiny imunologie   MeSH
• proteiny vázající retinol imunologie   MeSH
• průtoková cytometrie MeSH
• regulační T-lymfocyty imunologie   MeSH
• retina imunologie   MeSH
• retinitida chemicky indukované   etiologie   imunologie   mikrobiologie   MeSH
• uveitida chemicky indukované   imunologie   mikrobiologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• Názvy látek
• antibakteriální látky MeSH
• autoantigeny MeSH
• interferon gama MeSH
• interleukin-17 MeSH
• interstitial retinol-binding protein MeSH Prohlížeč
• oční proteiny MeSH
• proteiny vázající retinol MeSH

BACKGROUND: Ankylosing enthesopathy (ANKENT) is an animal model of human ankylosing spondylitis. ANKENT is an inflammatory disease affecting the ankle and tarsal joints of the hind limbs in susceptible mouse strains. In the disease, the participation of intestinal microbiota components was suggested. Therefore, we attempted to increase the incidence of ANKENT by systemic administration of lipopolysaccharide (LPS), which is a component of bacterial cellular walls and stimulates inflammatory processes. METHODS: ANKENT occurrence, serum cytokine profiles, spleen cellular composition and in vitro cytokine response to LPS were analysed in LPS-treated and control LPS-untreated B10.BR male mice. RESULTS: Contrary to expectations, LPS treatment decreased the incidence of ANKENT in LPS-treated group compared to control LPS-untreated group. Flow cytometry analysis of splenocytes showed an increased percentage of macrophages, dendritic cells and neutrophils and a decreased percentage of B cells, T cells and T helper cells in LPS-treated males following LPS administration. In addition, LPS-treated males had significantly elevated IL-6 and IL-10 serum levels. At 20-22 weeks after the final LPS application, splenocytes from LPS-treated mice were more susceptible to in vitro LPS stimulation than those of the controls and produced significantly higher levels of TNFα and IL-6. CONCLUSIONS: Repeated systemic stimulation with microbial component lipopolysaccharide in early adulthood significantly reduced the incidence of ANKENT in B10.BR mice and this finding can support the "hygiene hypothesis". In LPS-treated mice, the innate immunity parameters and the level of anti-inflammatory IL-10 cytokine were significantly increased. Nevertheless, the immunological mechanism of the LPS protective effect remains unclear.

• MeSH
• ankylózující spondylitida krev   imunologie   prevence a kontrola   MeSH
• časové faktory MeSH
• injekce intraperitoneální MeSH
• interleukin-10 krev   MeSH
• interleukin-6 krev   MeSH
• kultivované buňky MeSH
• lipopolysacharidy aplikace a dávkování   farmakologie   MeSH
• lymfocyty účinky léků   imunologie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• přirozená imunita účinky léků   MeSH
• průtoková cytometrie MeSH
• slezina účinky léků   imunologie   MeSH
• TNF-alfa metabolismus   MeSH
• upregulace MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• IL10 protein, mouse MeSH Prohlížeč
• interleukin-10 MeSH
• interleukin-6 MeSH
• lipopolysacharidy MeSH
• TNF-alfa MeSH

Metagenomic approaches are currently being used to decipher the genome of the microbiota (microbiome), and, in parallel, functional studies are being performed to analyze the effects of the microbiota on the host. Gnotobiological methods are an indispensable tool for studying the consequences of bacterial colonization. Animals used as models of human diseases can be maintained in sterile conditions (isolators used for germ-free rearing) and specifically colonized with defined microbes (including non-cultivable commensal bacteria). The effects of the germ-free state or the effects of colonization on disease initiation and maintenance can be observed in these models. Using this approach we demonstrated direct involvement of components of the microbiota in chronic intestinal inflammation and development of colonic neoplasia (i.e., using models of human inflammatory bowel disease and colorectal carcinoma). In contrast, a protective effect of microbiota colonization was demonstrated for the development of autoimmune diabetes in non-obese diabetic (NOD) mice. Interestingly, the development of atherosclerosis in germ-free apolipoprotein E (ApoE)-deficient mice fed by a standard low-cholesterol diet is accelerated compared with conventionally reared animals. Mucosal induction of tolerance to allergen Bet v1 was not influenced by the presence or absence of microbiota. Identification of components of the microbiota and elucidation of the molecular mechanisms of their action in inducing pathological changes or exerting beneficial, disease-protective activities could aid in our ability to influence the composition of the microbiota and to find bacterial strains and components (e.g., probiotics and prebiotics) whose administration may aid in disease prevention and treatment.

• MeSH
• autoimunitní nemoci etiologie   mikrobiologie   MeSH
• gastrointestinální trakt mikrobiologie   MeSH
• gnotobiologické modely * MeSH
• imunita MeSH
• lidé MeSH
• metagenom imunologie   MeSH
• modely nemocí na zvířatech MeSH
• nádory etiologie   mikrobiologie   MeSH
• sliznice imunologie   MeSH
• zánět etiologie   mikrobiologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

BACKGROUND: Ankylosing enthesopathy (ANKENT) with progressive stiffening of ankle and tarsal joints of the hind limbs is a naturally occurring arthropathy in B10.BR mice. Some features are similar to those of the spondyloarthropathies in humans. OBJECTIVE: To study the role of sexual dimorphism and testosterone in the development of ANKENT. METHODS: The incidence of ANKENT was observed in non-castrated, castrated, and testosterone substituted castrated male mice, and in control and testosterone treated female mice. RESULTS: ANKENT occurred only in males; it did not develop in males castrated at age 2-3 months but occurred in castrated males injected with testosterone. Females injected with testosterone did not develop ANKENT. CONCLUSION: Testosterone can replace what castration eliminates, at least in the postpubertally castrated males, but is itself not sufficient to induce joint disease.

• MeSH
• ankylóza krev   patofyziologie   MeSH
• lidé MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• orchiektomie MeSH
• pohlavní dimorfismus * MeSH
• testosteron krev   fyziologie   MeSH
• zadní končetina * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• testosteron MeSH

A possible relationship between intestinal inflammation and joint disease development was investigated. Clinical symptoms of colitis--diarrhea and rectal bleeding--were confirmed by findings of inflammatory processes in the colon in dextran sodium sulfate-treated mice and joint ankylosing enthesopathy (ANKENT) developed in 12.8 % mice with chronic colitis and 13.6 % mice in the control group. Consequently no significant difference in ANKENT frequency was found between mice with and without chronic colitis and the occurrence of ANKENT in both groups was typical for conventional conditions. ANKENT cannot be triggered solely a generalized inflammatory process in the gut.

• MeSH
• ankylóza epidemiologie   etiologie   MeSH
• klouby nohy (od hlezna dolů) patologie   MeSH
• kolon patologie   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• prevalence MeSH
• síran dextranu škodlivé účinky   MeSH
• ulcerózní kolitida chemicky indukované   komplikace   patologie   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• síran dextranu MeSH