Hanisch, Uwe-Karsten

[["dc.bibliographiccitation.artnumber","39"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Neuroinflammation"],["dc.bibliographiccitation.volume","18"],["dc.contributor.author","Ribes, S."],["dc.contributor.author","Zacke, L."],["dc.contributor.author","Nessler, S."],["dc.contributor.author","Saiepour, N."],["dc.contributor.author","Avendaño-Guzmán, E."],["dc.contributor.author","Ballüer, M."],["dc.contributor.author","Hanisch, U. K."],["dc.contributor.author","Nau, R."],["dc.date.accessioned","2021-04-14T08:28:08Z"],["dc.date.accessioned","2022-08-16T13:10:55Z"],["dc.date.available","2021-04-14T08:28:08Z"],["dc.date.available","2022-08-16T13:10:55Z"],["dc.date.issued","2021-02-02"],["dc.date.updated","2022-07-29T12:17:30Z"],["dc.description.abstract","Background\r\n Bacterial meningitis is a fatal disease with a mortality up to 30% and neurological sequelae in one fourth of survivors. Available vaccines do not fully protect against this lethal disease. Here, we report the protective effect of synthetic oligodeoxynucleotides containing unmethylated cytosine-guanine motifs (CpG ODN) against the most frequent form of bacterial meningitis caused by Streptococcus pneumoniae.\r\n \r\n \r\n Methods\r\n Three days prior to the induction of meningitis by intracerebral injection of S. pneumoniae D39, wild-type and Toll-like receptor (TLR9)−/− mice received an intraperitoneal injection of 100 μg CpG ODN or vehicle. To render mice neutropenic, anti-Ly-6G monoclonal antibody was daily administrated starting 4 days before infection with a total of 7 injections. Kaplan-Meier survival analyses and bacteriological studies, in which mice were sacrificed 24 h and 36 h after infection, were performed.\r\n \r\n \r\n Results\r\n Pre-treatment with 100 μg CpG ODN prolonged survival of immunocompetent and neutropenic wild-type mice but not of TLR9−/− mice. There was a trend towards lower mortality in CpG ODN-treated immunocompetent and neutropenic wild-type mice. CpG ODN caused an increase of IL-12/IL-23p40 levels in the spleen and serum in uninfected animals. The effects of CpG ODN on bacterial concentrations and development of clinical symptoms were associated with an increased number of microglia in the CNS during the early phase of infection. Elevated concentrations of IL-12/IL-23p40 and MIP-1α correlated with lower bacterial concentrations in the blood and spleen during infection.\r\n \r\n \r\n Conclusions\r\n Pre-conditioning with CpG ODN strengthened the resistance of neutropenic and immunocompetent mice against S. pneumoniae meningitis in the presence of TLR9. Administration of CpG ODN decreased bacterial burden in the cerebellum and reduced the degree of bacteremia. Systemic administration of CpG ODN may help to prevent or slow the progression to sepsis of bacterial CNS infections in healthy and immunocompromised individuals even after direct inoculation of bacteria into the intracranial compartments, which can occur after sinusitis, mastoiditis, open head trauma, and surgery, including placement of an external ventricular drain."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2021"],["dc.identifier.citation","Journal of Neuroinflammation. 2021 Feb 02;18(1):39"],["dc.identifier.doi","10.1186/s12974-021-02077-3"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17725"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82510"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112768"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.notes.intern","Merged from goescholar"],["dc.relation.eissn","1742-2094"],["dc.relation.orgunit","Institut für Neuropathologie"],["dc.rights","CC BY 4.0"],["dc.rights.holder","The Author(s)"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject","Oligodeoxynucleotides containing unmethylated cytosine-guanine motifs (CpG ODN)"],["dc.subject","Streptococcus pneumoniae"],["dc.subject","Meningitis"],["dc.subject","Toll-like receptor (TLR) 9"],["dc.subject","Interleukin (IL)-12/IL-23p40"],["dc.subject","Microglia"],["dc.subject","Macrophage inflammatory protein (MIP)-1α"],["dc.title","Oligodeoxynucleotides containing unmethylated cytosine-guanine motifs are effective immunostimulants against pneumococcal meningitis in the immunocompetent and neutropenic host"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","15482"],["dc.bibliographiccitation.issue","17"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","15493"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Rietkötter, Eva"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Bayerlová, Michaela"],["dc.contributor.author","Menck, Kerstin"],["dc.contributor.author","Chuang, Han-Ning"],["dc.contributor.author","Wenske, Britta"],["dc.contributor.author","Schwartz, Hila"],["dc.contributor.author","Erez, Neta"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.contributor.author","Pukrop, Tobias"],["dc.date.accessioned","2019-07-09T11:42:37Z"],["dc.date.available","2019-07-09T11:42:37Z"],["dc.date.issued","2015-06-20"],["dc.description.abstract","The mononuclear phagocytic system is categorized in three major groups: monocyte-derived cells (MCs), dendritic cells and resident macrophages. During breast cancer progression the colony stimulating factor 1 (CSF-1) can reprogram MCs into tumor-promoting macrophages in the primary tumor. However, the effect of CSF-1 during colonization of the brain parenchyma is largely unknown. Thus, we analyzed the outcome of anti-CSF-1 treatment on the resident macrophage population of the brain, the microglia, in comparison to MCs, alone and in different in vitro co-culture models. Our results underline the addiction of MCs to CSF-1 while surprisingly, microglia were not affected. Furthermore, in contrast to the brain, the bone marrow did not express the alternative ligand, IL-34. Yet treatment with IL-34 and co-culture with carcinoma cells partially rescued the anti-CSF-1 effects on MCs. Further, MC-induced invasion was significantly reduced by anti-CSF-1 treatment while microglia-induced invasion was reduced to a lower extend. Moreover, analysis of lung and breast cancer brain metastasis revealed significant differences of CSF-1 and CSF-1R expression. Taken together, our findings demonstrate not only differences of anti-CSF-1 treatment on MCs and microglia but also in the CSF-1 receptor and ligand expression in brain and bone marrow as well as in brain metastasis."],["dc.identifier.doi","10.18632/oncotarget.3855"],["dc.identifier.fs","618466"],["dc.identifier.pmid","26098772"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13609"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58709"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1949-2553"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.subject.mesh","Animals"],["dc.subject.mesh","Antibodies, Monoclonal"],["dc.subject.mesh","Brain"],["dc.subject.mesh","Brain Neoplasms"],["dc.subject.mesh","Breast Neoplasms"],["dc.subject.mesh","Cell Line, Tumor"],["dc.subject.mesh","Cell Movement"],["dc.subject.mesh","Cell Proliferation"],["dc.subject.mesh","Female"],["dc.subject.mesh","Humans"],["dc.subject.mesh","Interleukin-1"],["dc.subject.mesh","MCF-7 Cells"],["dc.subject.mesh","Macrophage Colony-Stimulating Factor"],["dc.subject.mesh","Macrophages"],["dc.subject.mesh","Mice"],["dc.subject.mesh","Mice, Inbred BALB C"],["dc.subject.mesh","Microglia"],["dc.subject.mesh","Monocytes"],["dc.subject.mesh","Neoplasm Invasiveness"],["dc.subject.mesh","Receptor, Macrophage Colony-Stimulating Factor"],["dc.title","Anti-CSF-1 treatment is effective to prevent carcinoma invasion induced by monocyte-derived cells but scarcely by microglia."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1449"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","1460"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","Rietkötter, Eva"],["dc.contributor.author","Menck, Kerstin"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Farhat, Katja"],["dc.contributor.author","Schaffrinski, Meike"],["dc.contributor.author","Schulz, Matthias"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Pukrop, Tobias"],["dc.date.accessioned","2019-07-10T08:11:45Z"],["dc.date.available","2019-07-10T08:11:45Z"],["dc.date.issued","2013-09-01"],["dc.description.abstract","The bisphosphonate zoledronic acid (ZA) significantly reduces complications of bone metastasis by inhibiting resident macrophages, the osteoclasts. Recent clinical trials indicate additional anti-metastatic effects of ZA outside the bone. However, which step of metastasis is influenced and whether thisis due to directtoxicity on cancer cells or inhibition of the tumor promoting microenvironment, is unknown. In particular, tumor-associated and resident macrophages support each step of organ metastasis and could be a crucial target of ZA. Thus, we comparatively investigate the ZA effects on: i) different types of macrophages, ii) on breast cancer cells but also iii) on macrophage-induced invasion. We demonstrate that ZA concentrations reflecting the plasma level affected viability of human macrophages, murine bone marrow-derived macrophages as well as their resident brain equivalents, the microglia, while it did not influence the tested cancer cells. However, the effects on the macrophages subsequently reduced the macrophage/microglia-induced invasiveness of the cancer cells. In line with this, manipulation of microglia by ZA in organotypic brain slice cocultures reduced the tissue invasion by carcinoma cells. The characterization of human macrophages after ZA treatment revealed a phenotype/response shift, in particular after external stimulation. In conclusion, we show that therapeutic concentrations of ZA affect all types of macrophages but not the cancer cells. Thus, anti-metastatic effects of ZA are predominantly caused by modulating the microenvironment. Most importantly, our findings demonstrate that ZA reduced microglia-assisted invasion of cancer cells to the brain tissue, indicating a potential therapeutic role in the prevention of cerebral metastasis."],["dc.identifier.fs","599082"],["dc.identifier.pmid","24036536"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10758"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60792"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1949-2553"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","CC BY 3.0"],["dc.rights.uri","http://creativecommons.org/licenses/by/3.0"],["dc.subject.mesh","Animals"],["dc.subject.mesh","Breast Neoplasms"],["dc.subject.mesh","Cell Communication"],["dc.subject.mesh","Cell Line, Tumor"],["dc.subject.mesh","Cell Proliferation"],["dc.subject.mesh","Coculture Techniques"],["dc.subject.mesh","Diphosphonates"],["dc.subject.mesh","Female"],["dc.subject.mesh","Humans"],["dc.subject.mesh","Imidazoles"],["dc.subject.mesh","MCF-7 Cells"],["dc.subject.mesh","Macrophages"],["dc.subject.mesh","Matrix Metalloproteinases"],["dc.subject.mesh","Mice"],["dc.subject.mesh","Microglia"],["dc.subject.mesh","Tumor Microenvironment"],["dc.title","Zoledronic acid inhibits macrophage/microglia-assisted breast cancer cell invasion."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]