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UWE-KARSTEN HEYE, Los Benjamin. Una familia alemana, Trotta, Madrid, 2020
No full textUWE-KARSTEN HEYE, Los Benjamin. Una familia alemana, Trotta, Madrid, 2020
Functional diversity of microglia – How heterogeneous are they to begin with?
No full textMicroglia serve in the surveillance and maintenance, protection and restoration of the CNS homeostasis. By their parenchymal location they differ from other CNS-associated myeloid cells, and by origin as well as functional characteristics they are also‒at least in part‒distinct from extraneural tissue macrophages. Nevertheless, microglia themselves may not comprise a uniform cell type. CNS regions vary by cellular and chemical composition, including white matter (myelin) content, blood-brain barrier properties or prevaling neurotransmitters. Such a micromilieu could instruct as well as require local adaptions of microglial features. Yet even cells within circumscribed populations may reveal some specialization by subtypes, regarding house-keeping duties and functional capacities upon challenges. While diversity of reactive phenotypes has been established still little is known as to whether all activated cells would respond with the same program of induced genes and functions or whether responder subsets have individual contributions. Preferential synthesis of a key cytokine could asign a master control to certain cells among a pool of activated microglia. Critical functions could be sequestered to discrete microglial subtypes in order to avoid interference, such as clearance of endogeneous material and presentation of antigens. Indeed, several and especially a number of recent studies provide evidence for the constitutive and reactive heterogeneity of microglia by and within CNS regions. While such a principle of ‘division of labor’ would influence the basic notion of ‘the’ microglia, it could come with the practival value of addressing separate microglia types in experimental and therapeutic manipulations
Proteins in Microglial Activation - Inputs and Outputs by Subsets
No full textMicroglia serve in the surveillance, maintenance and protection of the central nervous system (CNS) homeostasis and functionality. The process of transformation from their house-keeping status to reactive phenotypes upon CNS challenges is known as microglial activation. It comes also with dramatic changes in protein expression and release. Activated microglia may thereby mount a rather homogenous response, with all cells of an affected local population simultaneously upregulating the same cell surface receptors or synthesizing an identical set of soluble messengers. Yet there is increasing evidence for a constitutive heterogeneity of microglia by and within CNS regions-largely being based on protein expression as well as activities and pointing to distinct functional capacities as to microglial subtypes. Inductions of proteins with key functions in antigen presentation and inflammation, like major histocompatibility complex (MHC) class I or II molecules and tumor necrosis factor (TNF) alpha, reveal that among a pool of activated microglia individual cells can differ by actual contributions. While MHC I induction can be appropriately triggered as a panpopulational response, only a subset would organize for TNF production. Similarly, MHC II expression seems to be confined to a microglial subpopulation, and disposal of myelin either under normal conditions or its removal upon CNS damage appear to be duties of specialized cells, partially with complementary distribution. Discrete synthesis of immunoregulatory proteins would thus assign a master control to certain microglia, while tasks in the clearance of endogenous material and in professional antigen presentation could be sequestered to avoid collision of incompatible functions
Linking STAT and TLR signaling in microglia: a new role for the histone demethylase Jmjd3
No full textMicroglial diversity by responses and responders
No full textMicroglia are the principal resident innate immune cells of the CNS. Their contributions to the normal development of the CNS, the maintenance and plasticity of neuronal networks and the safeguarding of proper functionality are becoming more and more evident. Microglia also survey the tissue homeostasis to respond rapidly to exogenous and endogenous threats, primarily with a protective outcome. However, excessive acute activation, chronic activity or an improper adaption of their functional performance can foster neuropathologies. A key to the versatile response behavior of these cells is their ability to commit to reactive phenotypes, which reveal enormous complexity. Yet the respective profiles of induced genes and installed functions may build up on heterogeneous contributions of cellular subsets. Here, we discuss findings and concepts that consider the variety of microglial activities and response options as being based―at least in part―on a diversity of the engaged cells. Whether it is the production of proinflammatory cytokines, clearance of tissue debris, antigen presentation or the ability to sense neurotransmitters, microglial cells present with an unanticipated heterogeneity of their constitutive and inducible features. While the organizational principles of this heterogeneity are still largely unknown, functional implications are already perceptible
The crucial impact of the unique organ-specific defense system during colonization and outgrowth of brain metastasis
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