IL-1 type I receptor plays a key role in mediating the recruitment of leukocytes into the central nervous system

ABSTRACTStrain type is one of the key factors suspected to play a role in determining the outcome ofToxoplasmainfection. In this study, we examined the transcriptional profile of human neuroepithelioma cells in response to representative strains ofToxoplasmaby using microarray analysis to characterize the strain-specific host cell response. The study of neural cells is of interest in light of the ability ofToxoplasmato infect the brain and to establish persistent infection within the central nervous system. We found that the extents of the expression changes varied considerably among the three strains. Neuroepithelial cells infected withToxoplasmatype I exhibited the highest level of differential gene expression, whereas type II-infected cells had a substantially smaller number of genes which were differentially expressed. Cells infected with type III exhibited intermediate effects on gene expression. The three strains also differed in the individual genes and gene pathways which were altered following cellular infection. For example, gene ontology (GO) analysis indicated that type I infection largely affects genes related to the central nervous system, while type III infection largely alters genes which affect nucleotide metabolism; type II infection does not alter the expression of a clearly defined set of genes. Moreover, Ingenuity Pathways Analysis (IPA) suggests that the three lineages differ in the ability to manipulate their host; e.g., they employ different strategies to avoid, deflect, or subvert host defense mechanisms. These observed differences may explain some of the variation in the neurobiological effects of different strains ofToxoplasmaon infected individuals.

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THE PATHOGENESIS AND PATHWAY INTO THE CENTRAL NERVOUS SYSTEM AFTER INTRAOCULAR INFECTION OF HERPES SIMPLEX VIRUS TYPE I IN RABBITS

Neuropathology and Applied Neurobiology ◽

10.1111/j.1365-2990.1978.tb00554.x ◽

1978 ◽

Vol 4 (2) ◽

pp. 137-150 ◽

Cited By ~ 18

Author(s):

H. K. NARANG ◽

A. A. CODD

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Herpes Simplex Virus ◽

Herpes Simplex ◽

Virus Type ◽

Herpes Simplex Virus Type ◽

Type I ◽

The Central Nervous System ◽

Simplex Virus

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Cellular mechanisms of muscle fatigue

Physiological Reviews ◽

10.1152/physrev.1994.74.1.49 ◽

1994 ◽

Vol 74 (1) ◽

pp. 49-94 ◽

Cited By ~ 761

Author(s):

R. H. Fitts

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Muscle Fatigue ◽

Fiber Type ◽

Type I ◽

Fiber Types ◽

Force Frequency ◽

Frequency Curve ◽

Tension Development ◽

The Central Nervous System

Fatigue, defined as the failure to maintain the required or expected power output, is a complex problem, since multiple factors are clearly involved, with the relative importance of each dependent on the fiber type composition of the contracting muscles(s), and the intensity, type, and duration of the contractile activity. The primary sites of fatigue appear to be within the muscle cell itself and for the most part do not involve the central nervous system or the neuromuscular junction. The major hypotheses of fatigue center on disturbances in the surface membrane, E-C coupling, or metabolic events. The cell sites most frequently linked to the etiology of skeletal muscle fatigue are shown in Figure 1. Skeletal muscles are composed of at least four distinct fiber types (3 fast twitch and 1 slow twitch), with the slow type I and fast type IIa fibers containing the highest mitochondrial content and fatigue resistance. Despite fiber type differences in the degree of fatigability, the contractile properties undergo characteristic changes with the development of fatigue that can be observed in whole muscles, single motor units, and single fibers. The Po declines, and the contraction and relaxation times are prolonged. Additionally, there is a decrease in the peak rate of tension development and decline and a reduced Vo. Changes in Vo are more resistant to fatigue than Po and are not observed until Po has declined by at least 10% of its initial prefatigued value. However, the reduced peak power by which fatigue is defined results from both a reduction in Vo and Po. In the absence of muscle fiber damage, the prolonged relaxation time associated with fatigue causes the force-frequency curve to shift to the left, such that peak tensions are obtained at lower frequencies of stimulation. In a mechanism not clearly understood, the central nervous system senses this condition and reduces the alpha-motor nerve activation frequency as fatigue develops. In some cases, selective LFF develops that displaces the force-frequency curve to the right. Although not proven, it appears likely that this condition is associated with and likely caused by muscle injury, such that the SR releases less Ca2+ at low frequencies of activation. Alternatively, LFF could result from a reduced membrane excitability, such that the sarcolemma action potential frequency is considerably less than the stimulation frequency.(ABSTRACT TRUNCATED AT 400 WORDS)

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Detection of human T-lymphotropic virus type I (HTLV-I) tax RNA in the central nervous system of HTLV-I-associated myelopathy/tropical spastic paraparesis patients by in situ hybridization

Annals of Neurology ◽

10.1002/ana.410370206 ◽

1995 ◽

Vol 37 (2) ◽

pp. 167-175 ◽

Cited By ~ 103

Author(s):

Tanya J. Lehky ◽

Michael C. Levin ◽

Nick Flerlage ◽

Steven Jacobson ◽

Cecil H. Fox ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

In Situ Hybridization ◽

Virus Type ◽

Spastic Paraparesis ◽

Tropical Spastic Paraparesis ◽

Type I ◽

T Lymphotropic Virus ◽

The Central Nervous System

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In situ histochemical localization of type I interleukin-1 receptor messenger RNA in the central nervous system, pituitary, and adrenal gland of the mouse

Journal of Neuroscience ◽

10.1523/jneurosci.12-03-01101.1992 ◽

1992 ◽

Vol 12 (3) ◽

pp. 1101-1114 ◽

Cited By ~ 237

Author(s):

ET Cunningham ◽

E Wada ◽

DB Carter ◽

DE Tracey ◽

JF Battey ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Adrenal Gland ◽

Messenger Rna ◽

Interleukin 1 ◽

Histochemical Localization ◽

Type I ◽

The Central Nervous System

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Type I Interferon Receptor Signaling Drives Selective Permissiveness of Astrocytes and Microglia to Measles Virus during Brain Infection

Journal of Virology ◽

10.1128/jvi.00618-19 ◽

2019 ◽

Vol 93 (13) ◽

Cited By ~ 5

Author(s):

Jeremy Charles Welsch ◽

Benjamin Charvet ◽

Sebastien Dussurgey ◽

Omran Allatif ◽

Noemie Aurine ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Measles Virus ◽

Type I Interferon ◽

Proteome Analysis ◽

Secreted Proteins ◽

Type I ◽

Brain Infection ◽

The Central Nervous System

ABSTRACTFatal neurological syndromes can occur after measles virus (MeV) infection of the brain. The mechanisms controlling MeV spread within the central nervous system (CNS) remain poorly understood. We analyzed the role of type I interferon (IFN-I) receptor (IFNAR) signaling in the control of MeV infection in a murine model of brain infection. Using organotypic brain cultures (OBC) from wild-type and IFNAR-knockout (IFNARKO) transgenic mice ubiquitously expressing the human SLAM (CD150) receptor, the heterogeneity of the permissiveness of different CNS cell types to MeV infection was characterized. In the absence of IFNAR signaling, MeV propagated significantly better in explant slices. In OBC from IFNAR-competent mice, while astrocytes and microglia were infected on the day of explant preparation, they became refractory to infection with time, in contrast to neurons and oligodendrocytes, which remained permissive to infection. This selective loss of permissiveness to MeV infection was not observed in IFNARKOmouse OBC. Accordingly, the development of astrogliosis related to the OBC procedure was exacerbated in the presence of IFNAR signaling. In the hippocampus, this astrogliosis was characterized by a change in the astrocyte phenotype and by an increase of IFN-I transcripts. A proteome analysis showed the upregulation of 84 out of 111 secreted proteins. In the absence of IFNAR, only 27 secreted proteins were upregulated, and none of these were associated with antiviral activities. Our results highlight the essential role of the IFN-I response in astrogliosis and in the permissiveness of astrocytes and microglia that could control MeV propagation throughout the CNS.IMPORTANCEMeasles virus (MeV) can infect the central nervous system (CNS), with dramatic consequences. The mechanisms controlling MeV invasion of the CNS remain ill-defined since most previous data were obtained from postmortem analysis. Here, we highlight for the first time the crucial role of the type I interferon (IFN-I) response not only in the control of CNS invasion but also in the early permissiveness of glial cells to measles virus infection.

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The Innate Immune Adaptor Molecule MyD88 Restricts West Nile Virus Replication and Spread in Neurons of the Central Nervous System

Journal of Virology ◽

10.1128/jvi.01026-10 ◽

2010 ◽

Vol 84 (23) ◽

pp. 12125-12138 ◽

Cited By ~ 76

Author(s):

Kristy J. Szretter ◽

Stephane Daffis ◽

Jigisha Patel ◽

Mehul S. Suthar ◽

Robyn S. Klein ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

West Nile Virus ◽

Virus Replication ◽

Independent Effect ◽

Type I ◽

Rna Helicases ◽

West Nile ◽

The Central Nervous System ◽

The Brain

ABSTRACT Type I interferons (IFN-α/β) control viral infection by triggering the expression of genes that restrict transcription, translation, replication, and assembly. Many viruses induce IFN responses after recognition by cytoplasmic or endosomal RNA sensors (RIG-I-like RNA helicases [RLR] and Toll-like receptors [TLR]), which signal through the cognate adaptor signaling molecules IPS-1, TRIF, and MyD88. Recent studies have demonstrated that IPS-1-dependent induction of IFN-α/β downstream of RLR recognition restricts West Nile virus (WNV) infection in many cell types, whereas TRIF-dependent TLR3 signaling limits WNV replication in neurons. Here, we examined the contribution of MyD88 signaling to the control of WNV by evaluating IFN induction and virus replication in genetically deficient cells and mice. MyD88 − / − mice showed increased lethality after WNV infection and elevated viral burden primarily in the brain, even though little effect on the systemic type I IFN response was observed. Intracranial inoculation studies corroborated these findings, as WNV spread more rapidly in the central nervous system of MyD88 − / − mice, and this phenotype preceded the recruitment of inflammatory leukocytes. In vitro, increased WNV replication was observed in MyD88 − / − macrophages and subsets of neurons but not in myeloid dendritic cells. MyD88 had an independent effect on recruitment of monocyte-derived macrophages and T cells into the brain that was associated with blunted induction of the chemokines that attract leukocytes. Our experiments suggest that MyD88 restricts WNV by inhibiting replication in subsets of cells and modulating expression of chemokines that regulate immune cell migration into the central nervous system.

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Innate Immune Sensing of Viruses and Its Consequences for the Central Nervous System

Viruses ◽

10.3390/v13020170 ◽

2021 ◽

Vol 13 (2) ◽

pp. 170

Author(s):

Hina Singh ◽

Jeffrey Koury ◽

Marcus Kaul

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Nerve Fibers ◽

Innate Immune ◽

Health Concern ◽

Type I ◽

Lectin Receptors ◽

The Central Nervous System ◽

Immune Sensing ◽

Innate Immune Sensing

Viral infections remain a global public health concern and cause a severe societal and economic burden. At the organismal level, the innate immune system is essential for the detection of viruses and constitutes the first line of defense. Viral components are sensed by host pattern recognition receptors (PRRs). PRRs can be further classified based on their localization into Toll-like receptors (TLRs), C-type lectin receptors (CLR), retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), NOD-like receptors (NLRs) and cytosolic DNA sensors (CDS). TLR and RLR signaling results in production of type I interferons (IFNα and -β) and pro-inflammatory cytokines in a cell-specific manner, whereas NLR signaling leads to the production of interleukin-1 family proteins. On the other hand, CLRs are capable of sensing glycans present in viral pathogens, which can induce phagocytic, endocytic, antimicrobial, and pro- inflammatory responses. Peripheral immune sensing of viruses and the ensuing cytokine response can significantly affect the central nervous system (CNS). But viruses can also directly enter the CNS via a multitude of routes, such as the nasal epithelium, along nerve fibers connecting to the periphery and as cargo of infiltrating infected cells passing through the blood brain barrier, triggering innate immune sensing and cytokine responses directly in the CNS. Here, we review mechanisms of viral immune sensing and currently recognized consequences for the CNS of innate immune responses to viruses.

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