Search results for "Immunity"
showing 10 items of 1537 documents
OTUB1 inhibits CNS autoimmunity by preventing IFN-γ-induced hyperactivation of astrocytes.
2019
Astrocytes are critical regulators of neuroinflammation in multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). Growing evidence indicates that ubiquitination of signaling molecules is an important cell‐intrinsic mechanism governing astrocyte function during MS and EAE. Here, we identified an upregulation of the deubiquitinase OTU domain, ubiquitin aldehyde binding 1 (OTUB1) in astrocytes during MS and EAE. Mice with astrocyte‐specific OTUB1 ablation developed more severe EAE due to increased leukocyte accumulation, proinflammatory gene transcription, and demyelination in the spinal cord as compared to control mice. OTUB1‐deficient astrocytes were hy…
Innate and adaptive immune responses in the CNS.
2015
Almost every disorder of the CNS is said to have an inflammatory component, but the precise nature of inflammation in the CNS is often imprecisely defined, and the role of CNS-resident cells is uncertain compared with that of cells that invade the tissue from the systemic immune compartment. To understand inflammation in the CNS, the term must be better defined, and the response of tissue to disturbances in homoeostasis (eg, neurodegenerative processes) should be distinguished from disorders in which aberrant immune responses lead to CNS dysfunction and tissue destruction (eg, autoimmunity). Whether the inflammatory tissue response to injury is reparative or degenerative seems to be depende…
Host microbiota constantly control maturation and function of microglia in the CNS.
2015
As the tissue macrophages of the CNS, microglia are critically involved in diseases of the CNS. However, it remains unknown what controls their maturation and activation under homeostatic conditions. We observed substantial contributions of the host microbiota to microglia homeostasis, as germ-free (GF) mice displayed global defects in microglia with altered cell proportions and an immature phenotype, leading to impaired innate immune responses. Temporal eradication of host microbiota severely changed microglia properties. Limited microbiota complexity also resulted in defective microglia. In contrast, recolonization with a complex microbiota partially restored microglia features. We determ…
Comprehensive analysis of expression, subcellular localization, and cognate pairing of SNARE proteins in oligodendrocytes
2009
Oligodendrocytes form the central nervous system myelin sheath by spiral wrapping of their plasma membrane around axons, necessitating a high rate of exocytic membrane addition to the growing myelin membrane. Membrane fusion is mediated by soluble N-ethylmaleimide-sensitive factor attachment protein receptor proteins (SNAREs), which act by specific pairing of vesicle (R)- and target (Q)-SNAREs. To characterize oligodendroglial SNAREs and their trafficking pathways, we performed a detailed expression analysis of SNAREs in differentiating cultured oligodendrocytes and myelin and determined their subcellular localization. Expression of the plasma membrane Q-SNAREs syntaxin 3, syntaxin 4, SNAP2…
IL-17 and related cytokines involved in the pathology and immunotherapy of multiple sclerosis: Current and future developments.
2014
Multiple sclerosis (MS), an autoimmune neurological disorder, is driven by self-reactive T helper (Th) cells. Research on the role of Th17 lymphocytes in MS pathogenesis has made significant progress in identifying various immunological as well as environmental factors that induce the differentiation and expansion of these cells, different subsets of Th17 cells with varying degrees of pathogenicity, and the role of the secreted effector cytokines. While approved therapies for MS offer significant benefit to patients, there remain unmet needs. Ongoing clinical trials aim to translate the advanced knowledge of Th17 cytokines to improved therapies. This review discusses the current status and …
IL-23-mediated mononuclear phagocyte crosstalk protects mice from Citrobacter rodentium-induced colon immunopathology.
2014
Gut homeostasis and mucosal immune defense rely on the differential contributions of dendritic cells (DC) and macrophages. Here we show that colonic CX3CR1+ mononuclear phagocytes are critical inducers of the innate response to Citrobacter rodentium infection. Specifically, the absence of IL-23 expression in macrophages or CD11b+ DC results in the impairment of IL-22 production and in acute lethality. Highlighting immunopathology as a death cause, infected animals are rescued by the neutralization of IL-12 or IFNγ. Moreover, mice are also protected when the CD103+ CD11b− DC compartment is rendered deficient for IL-12 production. We show that IL-12 production by colonic CD103+ CD11b− DC is r…
The Chemokine Networks in Sponges: Potential Roles in Morphogenesis, Immunity and Stem Cell Formation
2003
Porifera (sponges) are now well accepted as the phylum which branched off first from the common ancestor of all metazoans, the Urmetazoa. The transition to the Metazoa became possible because during this phase, cell-cell as well as cell-matrix adhesion molecules evolved which allowed the formation of a colonial stage of animals. The next prerequisite for the evolution to the Urmetazoa was the establishment of an effective immune system which, flanked by apoptosis, allowed the formation of a first level of individuation.
Advances in the understanding of mast cell function
2008
Mast cells were formerly thought to contribute mainly to, sometimes even, fatal allergic reactions through the release of biologically highly active cytokines, chemokines, lipid mediators, proteases and biogenic amines. This potential harmful response is triggered by crosslinking of cell-bound IgE by the respective allergen. This review updates our current understanding of the emerging roles of mast cells with an emphasis on their relevance in protective host immunity. The activation of mast cells independently of Immunoglobulin E can lead to the initiation of fast inflammatory reactions, which were shown to be life-saving in murine models of bacterial infections. Besides their critical fun…
Validation of the Tetracycline Regulatable Gene Expression System for the Study of the Pathogenesis of Infectious Disease
2011
Understanding the pathogenesis of infectious disease requires the examination and successful integration of parameters related to both microbial virulence and host responses. As a practical and powerful method to control microbial gene expression, including in vivo, the tetracycline-regulatable system has recently gained the favor of many investigative groups. However, some immunomodulatory effects of the tetracyclines, including doxycycline, could potentially limit its use to evaluate host responses during infection. Here we have used a well-established murine model of disseminated candidiasis, which is highly dependent on both the virulence displayed by the fungal cells and on the host im…
Yeast β-glucans and microalgal extracts modulate the immune response and gut microbiome in Senegalese sole (Solea senegalensis)
2019
One bottleneck to sustainability of fish aquaculture is the control of infectious diseases. Current trends include the preventive application of immunostimulants and prebiotics such as polysaccharides. The present study investigated how yeast β-glucan (Y), microalgal polysaccharide-enriched extracts (MAe) and whole Phaeodactylum tricornutum cells (MA) modulated the gut microbiome and stimulated the immune system in Senegalese sole (Solea senegalensis) when administered by oral intubation. Blood, intestine and spleen samples were taken at 3 h, 24 h, 48 h and 7 days after treatment. The short-term response (within 48 h after treatment) consisted of up-regulation of il1b and irf7 expression in…