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1.
Int J Med Microbiol ; 306(5): 310-315, 2016 Aug.
Article in English | MEDLINE | ID: mdl-26924753

ABSTRACT

Faecal microbiota transplantation has gained increasing attention over the last decade as various phenotypes could be transferred from a donor to a recipient in different animal models. Clinically, however, the sole indication with evidence from a randomized placebo controlled trial is refractory Clostridium difficile infection. Despite revealing successful clinical outcomes, questions concerning regulatory affairs, the identification of the best donor, the optimal mixture of the transplant as well as the preferred route of administration remain to be clarified even for this indication. Initiated by the idea that alterations in the composition of the intestinal microbiota are associated with intestinal inflammation in inflammatory bowel disease, several studies investigated whether faecal microbiota transplantation would be an equally suitable approach for these devastating disorders. Indeed, the available data indicate changes in the microbiota composition following faecal microbial transplantation depending on the degree of intestinal inflammation. Furthermore, first data even provide evidence that the transplantation of an "optimized" microbiota induces clinical remission in ulcerative colitis. However, despite these intriguing results it needs to be considered that not only "a cure of inflammation", but also risk factors and phenotypes including obesity can be transferred via faecal microbiota transplantation. Thus, a deeper understanding of the impact of a distinct microbiota composition is required before "designing" the optimal faecal microbiota transplant.


Subject(s)
Enterocolitis, Pseudomembranous/therapy , Fecal Microbiota Transplantation/methods , Inflammatory Bowel Diseases/therapy , Clinical Trials as Topic , Clostridioides difficile/isolation & purification , Fecal Microbiota Transplantation/adverse effects , Humans , Treatment Outcome
2.
Mucosal Immunol ; 9(5): 1205-17, 2016 09.
Article in English | MEDLINE | ID: mdl-26813346

ABSTRACT

CD101 exerts negative-costimulatory effects in vitro, but its function in vivo remains poorly defined. CD101 is abundantly expressed on lymphoid and myeloid cells in intestinal tissues, but absent from naïve splenic T cells. Here, we assessed the impact of CD101 on the course of inflammatory bowel disease (IBD). Using a T-cell transfer model of chronic colitis, we found that in recipients of naïve T cells from CD101(+/+) donors up to 30% of the recovered lymphocytes expressed CD101, correlating with an increased interleukin (IL)-2-mediated FoxP3 expression. Transfer of CD101(-/-) T cells caused more severe colitis and was associated with an expansion of IL-17-producing T cells and an enhanced expression of IL-2Rα/ß independently of FoxP3. The co-transfer of naïve and regulatory T cells (Treg) protected most effectively from colitis, when both donor and recipient mice expressed CD101. Although the expression of CD101 on T cells was sufficient for Treg-function and the inhibition of T-cell proliferation, sustained IL-10 production required additional CD101 expression by myeloid cells. Finally, in patients with IBD a reduced CD101 expression on peripheral and intestinal monocytes and CD4(+) T cells correlated with enhanced IL-17 production and disease activity. Thus, CD101 deficiency is a novel marker for progressive colitis and potential target for therapeutic intervention.


Subject(s)
Antigens, CD/immunology , Colitis, Ulcerative/immunology , Crohn Disease/immunology , Interleukin-17/immunology , Membrane Glycoproteins/immunology , T-Lymphocytes, Regulatory/immunology , Th17 Cells/immunology , Adoptive Transfer , Animals , Antigens, CD/genetics , Colitis, Ulcerative/genetics , Colitis, Ulcerative/pathology , Colon/immunology , Colon/pathology , Crohn Disease/genetics , Crohn Disease/pathology , Disease Models, Animal , Forkhead Transcription Factors/genetics , Forkhead Transcription Factors/immunology , Gene Expression Regulation , Humans , Interleukin-10/genetics , Interleukin-10/immunology , Interleukin-17/genetics , Interleukin-2/genetics , Interleukin-2/immunology , Interleukin-2 Receptor alpha Subunit/genetics , Interleukin-2 Receptor alpha Subunit/immunology , Interleukin-2 Receptor beta Subunit/genetics , Interleukin-2 Receptor beta Subunit/immunology , Intestinal Mucosa/immunology , Intestinal Mucosa/pathology , Lymphocyte Activation , Membrane Glycoproteins/genetics , Mice , Mice, Knockout , Severity of Illness Index , Signal Transduction , T-Lymphocytes, Regulatory/pathology , T-Lymphocytes, Regulatory/transplantation , Th17 Cells/pathology , Th17 Cells/transplantation
3.
Eur J Immunol ; 30(8): 2257-67, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10940917

ABSTRACT

We recently reported that the infection of macrophages with Leishmania major led to the release of type 1 interferons (IFN-alpha /beta ). Moreover, at day 1 of infection of mice with L. major, IFN-alpha /beta was required for the expression of type 2 (inducible) NO synthase (NOS2 or iNOS) which, however, was restricted to a few macrophages in the dermis. Here, we further characterized the regulation of NOS2 by IFN-alpha /beta. Macrophages that were either simultaneously or sequentially exposed to L. major promastigotes and IFN-alpha /beta expressed NOS2 and anti-leishmanial activity. In contrast, when high amounts of IFN-alpha /beta were used or when IFN-alpha /beta was added to the macrophages 2 h prior to the parasites, almost no induction of NOS2 was observed. After pretreatment with IFN-alpha /beta, tyrosine phosphorylation and nuclear DNA binding of Stat1alpha, the degradation of the NF-kappaB inhibitor (IkappaBalpha and beta), and the nuclear translocation of NF-kappaB were strongly impaired compared with macrophages exposed to IFN-alpha /beta and L. major simultaneously. Thus, IFN-alpha /beta exerts agonistic or antagonistic effects on the expression of NOS2 in macrophages infected with a microbial pathogen, depending on the sequence of the stimuli and the amount of IFN-alpha /beta added. The limited number of NOS2-positive macrophages at day 1 of infection in vivo might result from a blockage of non-infected macrophages by IFN-alpha /beta that is released by neighboring infected cells.


Subject(s)
Gene Expression Regulation, Enzymologic/drug effects , Interferon Type I/pharmacology , Leishmania major/immunology , Macrophages/enzymology , Nitric Oxide Synthase/genetics , Animals , DNA-Binding Proteins/physiology , Female , Macrophages/parasitology , Mice , Mice, Inbred C3H , Mice, Inbred C57BL , NF-kappa B/physiology , Nitric Oxide/biosynthesis , Nitric Oxide Synthase Type II , Phosphorylation , STAT1 Transcription Factor , Trans-Activators/physiology , Tyrosine/metabolism
4.
Magn Reson Imaging ; 16(4): 393-404, 1998 May.
Article in English | MEDLINE | ID: mdl-9665550

ABSTRACT

PURPOSE: To implement and evaluate the accuracy of non-invasive temperature mapping using MRI methods based on the chemical shift (CS) and T1 relaxation in media of various heterogeneity during focal (laser) and external thermal energy deposition. MATERIALS AND METHODS: All measurements were performed on a 1.5 T superconducting clinical scanner using the temperature dependence of the water proton chemical shift and the T1 relaxation time. Homogeneous gel and heterogeneous muscle phantoms were heated focally with a fiberoptic laser probe and externally of varying degree ex vivo by water circulating in a temperature range of 20-50 degrees C. Magnetic resonance imaging data were compared to simultaneously recorded fiberoptic temperature readings. RESULTS: Both methods provided accurate results in homogeneous media (turkey) with better accuracy for the chemical shift method (CS:+/-1.5 degrees C, T1:+/-2.0 degrees C). In gel, the accuracy with the CS method was +/-0.6 degrees C. The accuracy decreased in heterogeneous media containing fat (T1:+/-3.5 degrees C, CS: +5 degrees C). In focal heating of turkey muscle, the accuracy was within 1.5 degrees C with the T1 method. CONCLUSION: Temperature monitoring with the chemical shift provides better results in homogeneous media containing no fat. In fat tissue, the temperature calculation proved to be difficult.


Subject(s)
Body Temperature , Joints/physiology , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy/methods , Muscle, Skeletal/physiology , Animals , Image Processing, Computer-Assisted , Phantoms, Imaging , Reproducibility of Results , Swine , Thermography/methods , Turkeys
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