Search results for "Specific Pathogen-Free Organisms"
showing 10 items of 32 documents
Therapeutic Opportunities in Intestinal Microbiota–Virus Interactions
2018
The host microbiota has emerged a third player in interactions between hosts and viral pathogens. This opens new possibilities to use different tools to modulate the intestinal microbial composition, aimed at reducing the risk of or treating viral enteric infections.
STAT1 Isoforms Differentially Regulate NK Cell Maturation and Anti-tumor Activity
2020
Natural killer (NK) cells are important components of the innate immune defense against infections and cancers. Signal transducer and activator of transcription 1 (STAT1) is a transcription factor that is essential for NK cell maturation and NK cell-dependent tumor surveillance. Two alternatively spliced isoforms of STAT1 exist: a full-length STAT1α and a C-terminally truncated STAT1β isoform. Aberrant splicing is frequently observed in cancer cells and several anti-cancer drugs interfere with the cellular splicing machinery. To investigate whether NK cell-mediated tumor surveillance is affected by a switch in STAT1 splicing, we made use of knock-in mice expressing either only the STAT1α (S…
Perforin deficiency attenuates inflammation and tumor growth in colitis-associated cancer
2010
Background: Patients with inflammatory bowel disease (IBD) have a markedly increased risk to develop colon cancer, but there are only limited data about the host antitumor response in such colitis-associated cancer. In the present study we aimed at assessing the role of perforin-dependent effector mechanisms in the immune response in a murine model of colitis-associated colon cancer. Methods: Wildtype and perforin-deficient mice were analyzed in a mouse model of colitis-associated colon cancer using azoxymethane (AOM) and dextran sodium sulfate (DSS). Results: Tumors of wildtype mice showed infiltration of CD4+, CD8+ T cells, natural killer (NK) cells, high numbers of apoptotic cells, and e…
Mast Cells Infiltrating Inflamed or Transformed Gut Alternatively Sustain Mucosal Healing or Tumor Growth.
2015
Abstract Mast cells (MC) are immune cells located next to the intestinal epithelium with regulatory function in maintaining the homeostasis of the mucosal barrier. We have investigated MC activities in colon inflammation and cancer in mice either wild-type (WT) or MC-deficient (KitW-sh) reconstituted or not with bone marrow-derived MCs. Colitis was chemically induced with dextran sodium sulfate (DSS). Tumors were induced by administering azoxymethane (AOM) intraperitoneally before DSS. Following DSS withdrawal, KitW-sh mice showed reduced weight gain and impaired tissue repair compared with their WT littermates or KitW-sh mice reconstituted with bone marrow-derived MCs. MCs were localized i…
Tick saliva increases production of three chemokines including monocyte chemoattractant protein-1, a histamine-releasing cytokine
2014
Summary The effect of Ixodes ricinus tick saliva on the production of various cytokines and chemokines by mouse splenocytes was tested by a cytokine array. We demonstrated a strong upregulation of three chemokines, monocyte chemoattractant protein-1 (MCP-1), thymus-derived chemotactic agent 3 (TCA-3) and macrophage inflammatory protein 2 (MIP-2). MCP-1 could be induced by tick saliva itself. While TCA-3 and MIP-2 are engaged in Th2 polarization of the host immune response associated with tick feeding, MCP-1 may act as a histamine release factor, increasing blood flow into the feeding lesion thus facilitating tick engorgement in the late, rapid feeding phase.
Tolerance towards resident intestinal flora in mice is abrogated in experimental colitis and restored by treatment with interleukin-10 or antibodies …
1996
There is now increasing evidence that hyperresponsiveness towards intestinal flora is a crucial event in the pathogenesis of inflammatory bowel disease (IBD). In support of this hypothesis, we recently described in humans that tolerance exists towards indigenous intestinal flora but is broken in active IBD lesions. In the present study, we have attempted to transfer this model into mice from different genetic backgrounds (BALB/c, SJL/J, C3H/HeJ). We found that mononuclear cells from spleen, small bowel and large bowel of mice do not proliferate, i.e. are tolerant when exposed to bacterial sonicates derived from autologous intestine (BsA) but do proliferate, i.e. are immune when exposed to b…
MAPK3 deficiency drives autoimmunity via DC arming.
2010
DC are professional APC that instruct T cells during the inflammatory course of EAE. We have previously shown that MAPK3 (Erk1) is important for the induction of T-cell anergy. Our goal was to determine the influence of MAPK3 on the capacity of DC to arm T-cell responses in autoimmunity. We report that DC from Mapk3(-/-) mice have a significantly higher membrane expression of CD86 and MHC-II and--when loaded with the myelin oligodendrocyte glycoprotein--show a superior capacity to prime naive T cells towards an inflammatory phenotype than Mapk3(+/+) DC. Nonetheless and as previously described, Mapk3(-/-) mice were only slightly but not significantly more susceptible to myelin oligodendrocyt…
Mutated cylindromatosis gene affects the functional state of dendritic cells
2010
Cylindromatosis gene (CYLD) is a ubiquitously expressed deubiquitinating enzyme, which interacts with members of the NF-κB signaling pathway and attenuates NF-κB and JNK signaling. Here, we report that DC derived from transgenic mice, which solely express a naturally occurring CYLD isoform (CYLD(ex7/8)), display a higher content of nuclear RelB and express elevated levels of NF-κB family members as well as of known NF-κB-target genes comprising costimulatory molecules and pro-inflammatory cytokines, as compared with WT DC. Accordingly, unstimulated CYLD(ex7/8) DC exhibited a significantly higher primary allogenic T-cell stimulatory capacity than WT DC and exerted no tolerogenic activity. Tr…
The viral chemokine MCK-2 of murine cytomegalovirus promotes infection as part of a gH/gL/MCK-2 complex.
2013
Human cytomegalovirus (HCMV) forms two gH/gL glycoprotein complexes, gH/gL/gO and gH/gL/pUL(128,130,131A), which determine the tropism, the entry pathways and the mode of spread of the virus. For murine cytomegalovirus (MCMV), which serves as a model for HCMV, a gH/gL/gO complex functionally homologous to the HCMV gH/gL/gO complex has been described. Knock-out of MCMV gO does impair, but not abolish, virus spread indicating that also MCMV might form an alternative gH/gL complex. Here, we show that the MCMV CC chemokine MCK-2 forms a complex with the glycoprotein gH, a complex which is incorporated into the virion. We could additionally show that mutants lacking both, gO and MCK-2 are not ab…