A5073050462- Neuroinflammation and Neurodegeneration Mechanisms
- Mosquito-borne diseases and control
- Viral Infections and Vectors
- Immune Response and Inflammation
- Vector-borne infectious diseases
- interferon and immune responses
- Neurogenesis and neuroplasticity mechanisms
- Viral Infections and Outbreaks Research
- T-cell and B-cell Immunology
- Immune cells in cancer
- Herpesvirus Infections and Treatments
- Malaria Research and Control
- Immune Cell Function and Interaction
- Cytomegalovirus and herpesvirus research
- Mesenchymal stem cell research
- Vector-Borne Animal Diseases
- Immunotherapy and Immune Responses
- Long-Term Effects of COVID-19
- Polyomavirus and related diseases
- Sphingolipid Metabolism and Signaling
- Multiple Sclerosis Research Studies
- Research on Leishmaniasis Studies
- Neonatal and Maternal Infections
- Inflammation biomarkers and pathways
- Neonatal and fetal brain pathology
University of Veterinary Medicine Hannover, Foundation
2021-2025
University of Veterinary Medicine
2023
Medizinische Hochschule Hannover
2010-2021
Helmholtz Centre for Infection Research
2018
Friedrich-Alexander-Universität Erlangen-Nürnberg
2011
Universitätsklinikum Erlangen
2011
Autoreactive Th1 and Th17 cells are believed to mediate the pathology of multiple sclerosis in central nervous system (CNS). Their interaction with microglia astrocytes CNS is crucial for regulation neuroinflammation. Previously, we have shown that only but not effectors activate microglia. However, it clear which targets CNS.To understand effects driven by CNS, induced experimental autoimmune encephalomyelitis wild-type mice CD4+ T cell-specific integrin α4-deficient where trafficking into...
In sterile neuroinflammation, a pathological role is proposed for microglia, whereas in viral encephalitis, their function not entirely clear. Many viruses exploit the odorant system and enter CNS via olfactory bulb (OB). Upon intranasal vesicular stomatitis virus instillation, we show an accumulation of activated microglia monocytes OB. Depletion during encephalitis results enhanced spread increased lethality. Activation, proliferation, are regulated by type I IFN receptor signaling neurons...
ABSTRACT Previously we found that following intranasal (i.n.) infection with neurotropic vesicular stomatitis virus (VSV) type I interferon receptor (IFNAR) triggering of neuroectodermal cells was critically required to constrain intracerebral spread. To address whether locally active IFN-β induced proximally, studied spatiotemporal conditions VSV-mediated induction. this end, performed studies reporter mice. One day after intravenous (i.v.) VSV infection, luciferase induction detected in...
Tick-borne encephalitis remains a significant burden on human health in the endemic areas Central Europe and Eastern Asia. The causative agent, tick-borne virus (TBEV), is neurotropic belonging to genus of Orthoflavivirus. After TBEV enters central nervous system (CNS), it mainly targets neurons, causing leading life-long disabilities, coma and, rare cases, death. neuroinvasive mechanisms orthoflaviviruses are poorly understood. Here we investigate mechanism neuroinvasion, hypothesizing that...
For the treatment of patients with multiple sclerosis there are no regenerative approaches to enhance remyelination. Mesenchymal stem cells (MSC) have been proposed exert such functions. Intravenous administration human MSC reduced clinical severity experimental autoimmune encephalomyelitis (EAE), an animal model mimicking some aspects sclerosis. However, it is not clear if this effect was achieved by systemic immunomodulation or active neuroregeneration in central nervous system (CNS). In...
Teriflunomide, an inhibitor of dihydroorotate dehydrogenase, is thought to ameliorate multiple sclerosis by reducing activation-induced proliferation lymphocytes, which highly dependent on de novo pyrimidine synthesis. Nevertheless, its immunomodulatory effects resident glial cells in the central nervous system are only poorly understood.In this study, we employed physiologically relevant concentrations teriflunomide and investigated survival, proliferation, activation, function primary rat...
Tick-borne encephalitis virus (TBEV) is one of the most relevant tick-transmitted neurotropic arboviruses in Europe and Asia causative agent tick-borne (TBE). Annually more than 10,000 TBE cases are reported despite having vaccines available. In Europe, FSME-IMMUN® Encepur® based on formaldehyde-inactivated whole viruses licensed. However, demanding vaccination schedules contribute to sub-optimal uptake breakthrough infections have been repeatedly. Due its immunogenic properties as well role...
ABSTRACT Natural killer (NK) cells are important components of a protective immune response against intracellular pathogens such as Leishmania parasites, which reside within myeloid cells. Previous in vivo studies murine cutaneous or visceral leishmaniasis showed that NK activated by conventional dendritic Toll-like receptor 9-, interleukin-12 (IL-12)-, and IL-18-dependent manner during the early phase infection help to restrict tissue parasite burden unknown mechanisms. Here, we tested...
Autoreactive T cells that infiltrate into the central nervous system (CNS) are believed to have a significant role in mediating pathology of neuroinflammatory diseases like multiple sclerosis. Their interaction with microglia and astrocytes CNS is crucial for regulation processes. Our previous work demonstrated effectors secreted by Th1 Th17 different capacities influence phenotype function glial cells. We shown Th1-derived altered both whereas Th17-derived induced direct effects only on but...
The property of DC to generate effective CTL responses is influenced by TLR signaling. ligands contain molecular signatures associated with pathogens, have an impact on the antigen processing and presentation DC, are being exploited as potential adjuvants. We hypothesized that TLR2/6 heterodimer agonist S-[2,3-bispalmitoyiloxy-(2R)-propyl]-R-cysteinyl-amido-monomethoxyl polyethylene glycol (BPP), a synthetic derivative Mycoplasma macrophage activating lipopeptide-2, potent adjuvant for...
Introduction Tick-borne encephalitis virus (TBEV) is an important human pathogen that can cause a serious disease involving the central nervous system (tick-borne encephalitis, TBE). Although approved inactivated vaccines are available, number of TBE cases rising, and breakthrough infections in fully vaccinated subjects have been reported recent years. Methods In present study, we generated characterized recombinant Modified Vaccinia Ankara (MVA) for delivery pre-membrane (prM) envelope (E)...
2-Chlorodeoxyadenosine (cladribine, CdA) is an immunosuppressive drug that licensed to treat hairy cell leukaemia, and has been shown recently have beneficial effects in patients with multiple sclerosis (MS). The therapeutic of CdA suggested be mediated partly through its potent toxicity towards lymphocytes. However, the on other immune cells are poorly understood. In present study, we investigated induction apoptosis human monocytes, monocyte-derived immature (ImDC) mature (mDC) dendritic...
Dimethylfumarate (DMF) has been approved the for treatment of relapsing-remitting multiple sclerosis. The mode action DMF and its assumed active primary metabolite monomethylfumarate (MMF) is still not fully understood, notably brain resident cells. Therefore we investigated potential direct effects MMF on microglia indirect oligodendrocytes. Primary rat were differentiated into M1-like, M2-like M0 phenotypes treated in vitro with or MMF. gene expression pro-inflammatory anti-inflammatory...
Naturally attenuated Langat virus (LGTV) and highly pathogenic tick-borne encephalitis (TBEV) share antigenically similar viral proteins are grouped together in the same flavivirus serocomplex. In early 1970s, this has encouraged usage of LGTV as a potential live vaccine against (TBE) until cases were reported among vaccinees. Previously, we have shown mouse model that immunity induced protects mice lethal TBEV challenge infection. However, immune correlates protection not been studied.We...
Dengue virus serotypes 1 to 4 (DENV1-4) place nearly half the global population at risk of infection and licenced tetravalent dengue vaccine fails protect individuals who have not previously been exposed DENV. The development intervention strategies had long hampered by lack a suitable small animal model. DENV does replicate in wild-type mice due its inability antagonise mouse type I interferon (IFN) response. Mice deficient IFN signalling (Ifnar1-/- mice) are highly susceptible infection,...
Tick-borne encephalitis (TBE) is a serious neurological disease caused by TBE virus (TBEV). Because antiviral treatment options are not available, vaccination the key prophylactic measure against TBEV infections. Despite availability of effective vaccines, cases breakthrough infections have been reported. The multienzymatic non-structural protein 3 (NS3) orthoflaviviruses plays an important role in polyprotein processing and replication. In present study, we evaluated NS3 as potential...
FTY720 is a new oral immunomodulatory therapy for the treatment of multiple sclerosis (MS). There strong evidence that has direct effects on brain resident cells such as astrocytes acting via sphingosine‑1‑phosphate (S1P) receptors. In present study, mRNA expression S1P receptors well selected cytokines, chemokines and growth factors were investigated in primary murine under inflammatory conditions presence or absence phosphorylated form (FTY720‑P). Following stimulation with either...
Perinatal inflammation causes immediate changes of the blood‐brain barrier (BBB) and thus may have different consequences in adult life including an impact on neurological diseases such as demyelinating disorders. In order to determine if a perinatal insult affects course demyelination adulthood “second hit,” we simulated bacterial by systemic administration lipopolysaccharide (LPS) either pregnant mice or newborn animals. Demyelination was later induced animals cuprizone [ bis...
Theiler's murine encephalomyelitis virus (TMEV) infection represents a commonly used infectious animal model to study various aspects of the pathogenesis multiple sclerosis (MS). In susceptible SJL mice, dominant activity Foxp3+ CD4+ regulatory T cells (Tregs) in CNS partly contributes viral persistence and progressive demyelination. On other hand, resistant C57BL/6 mice rapidly clear by mounting strong antiviral immune response. However, very little is known about role Tregs regulating...
Rift Valley fever (RVF) is a zoonotic and emerging disease, caused by the RVF virus (RVFV). In ruminants, it leads to “abortion storms” enhanced mortality rates in young animals, whereas humans can cause symptoms like severe hemorrhagic or encephalitis. The role of innate adaptive immune response disease initiation progression still poorly defined. present study used attenuated RVFV strain clone 13 investigate viral spread, tissue tropism, histopathological lesions after intranasal infection...
The four serotypes of dengue virus (DENV1–4) continue to pose a major public health threat. first licenced vaccine, which expresses the surface proteins DENV1–4, has performed poorly in immunologically naïve individuals, sensitising them antibody-enhanced disease. DENV non-structural protein 1 (NS1) can directly induce vascular leakage, hallmark severe disease, is blocked by NS1-specific antibodies, making it an attractive target for vaccine development. However, intrinsic ability NS1...