ABSTRACT
Gp130 is the common receptor of the IL-6 family of cytokines and is involved in many biological processes, including acute phase response, inflammation and immune reactions. To investigate the role of gp130 under inflammatory conditions, T-cell-specific conditional gp130 mice were first bred to the IL-10-deficient background and were then infected with the gastrointestinal nematode Trichuris muris. While IL-10(-/-) mice were highly susceptible to T. muris, developed a mixed Th1/Th17 response and displayed severe inflammation of the caecum, infection of mice with an additional T-cell-specific deletion of gp130 signalling completely reversed the phenotype. These mice showed an accelerated worm expulsion that was associated with the rapid generation of a strong Th2 immune response and a significant increase in Foxp3-expressing Treg. Therefore, gp130 signalling in T cells regulates a switch between proinflammatory and pathogenic Th1/Th17 cells and regulatory Th2/Treg in vivo. Taken together, the data demonstrate that gp130 signalling in T cells is a positive regulator of inflammatory processes, favouring the Th1/Th17 axis.
Subject(s)
Cytokine Receptor gp130/metabolism , Interleukin-10/metabolism , Intestinal Diseases, Parasitic/immunology , T-Lymphocytes/immunology , Trichinellosis/immunology , Animals , Cytokine Receptor gp130/genetics , Cytokines/metabolism , Female , Flow Cytometry , Forkhead Transcription Factors/metabolism , Host-Parasite Interactions , Immunity, Innate/immunology , Interleukin-10/genetics , Interleukin-17/metabolism , Intestinal Diseases, Parasitic/genetics , Intestinal Diseases, Parasitic/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Mice, Transgenic , Signal Transduction/immunology , T-Lymphocytes/metabolism , T-Lymphocytes/parasitology , T-Lymphocytes, Helper-Inducer/immunology , T-Lymphocytes, Helper-Inducer/metabolism , Th1 Cells/immunology , Th1 Cells/metabolism , Th2 Cells/immunology , Th2 Cells/metabolism , Trichinellosis/genetics , Trichinellosis/parasitology , Trichuris/physiologyABSTRACT
As recommendations for specific pathogen-free housing change, mouse facilities need to re-derive their colonies repeatedly in order to eliminate specified bacteria or viruses. This paper describes the establishment of a new mouse facility using as starting point a small colony of CD-1 mice colonized with the Charles River altered Schaedler flora (CRASF) housed in individually ventilated cages (IVCs). The import of new strains was performed exclusively via embryo transfer using CD-1 mice as recipients. The integrity of the CRASF in caecum samples of the original CD-1 colony and of three inbred mouse lines imported into the colony was proven by a quantitative realtime polymerase chain reaction approach. Furthermore, we searched for bacterial contaminants in the gut flora using non-specific 16S rRNA primers. The bacterial sequences found were closely related to but not exclusively sequences of altered Schaedler flora (ASF) members, suggesting that the ASF is heterogeneous rather than restricted to the eight defined bacteria. Moreover, no pathogens were found, neither using the non-specific 16S rRNA primers nor in routine quarterly health monitoring. As one effect of this defined gut flora, interleukin-10 knockout mice are devoid of colitis in our facility. In conclusion, our approach building up a mouse facility using foster mothers and embryo transfer as well as a strict barrier system and IVCs is suitable to maintain a colony free from contaminating bacteria over the long term. CRASF remained stable for seven mouse generations and was efficiently transferred to the imported mouse strains.
