RESUMO
Reactivation of herpes simplex virus 1 (HSV-1) from neurons in sensory ganglia such as the trigeminal ganglia (TG) is influenced by virus-specific CD8+ T cells that infiltrate the ganglia at the onset of latency and contract to a stable activated tissue-resident memory population. In C57BL/6 mice, half of HSV-specific CD8+ T cells (gB-CD8s) recognize one dominant epitope (residues 498 to 505) on glycoprotein B (gB498-505), while the remainder (non-gB-CD8s) recognize 19 subdominant epitopes from 12 viral proteins. To address how expression by HSV-1 influences the formation and ganglionic retention of CD8+ T cell populations, we developed recombinant HSV-1 with the native immunodominant gB epitope disrupted but then expressed ectopically from different viral promoters. In mice, the epitope expressed from the gB promoter restored full gB-CD8 immunodominance to 50%. Intriguingly, earlier expression from constitutive, immediate-early, and early promoters did not significantly increase immunodominance, indicating that these promoters cannot elicit more than half of the CD8 compartment. Epitope expressed from candidate viral promoters of "true late" HSV-1 genes either delayed or reduced the priming efficiency of gB-CD8s and their levels in the TG at early times. HSV expressing the epitope from the full latency-associated transcript promoter did not efficiently prime gB-CD8s; however, gB-CD8s primed by a concurrent wild-type flank infection infiltrated the TG and were retained long term, suggesting that latent epitope expression is sufficient to retain gB-CD8s. Taken together, the data indicate that viral promoters shape latent HSV-1-specific CD8+ T cell populations and should be an important consideration in future vaccine design.IMPORTANCE Latency of HSV-1 in host neurons enables long-term persistence from which reactivation may occur to cause recurrent diseases, such as blinding herpetic stromal keratitis. Latency is not antigenically silent, and viral proteins are sporadically expressed at low levels without full virion production. This protein expression is recognized by ganglion-resident HSV-1-specific CD8+ T cells that maintain a protective resident population. Since these T cells can influence lytic/latent decisions in reactivating neurons, we argue that improving their ganglionic retention and function may offer a strategy in vaccine design to reduce reactivation and recurrent disease. To understand factors driving the infiltration and retention of ganglionic CD8s, we examined several HSV recombinants that have different viral promoters driving expression of the immunodominant gB epitope. We show that the selection of epitope promoter influences CD8+ T cell population hierarchies and their function.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Gânglios/imunologia , Herpes Simples/imunologia , Herpesvirus Humano 1/imunologia , Epitopos Imunodominantes/imunologia , Animais , Chlorocebus aethiops , Modelos Animais de Doenças , Feminino , Gânglios Sensitivos/imunologia , Herpes Simples/virologia , Herpesvirus Humano 1/genética , Ceratite Herpética/imunologia , Cinética , Camundongos , Camundongos Endogâmicos C57BL , Gânglio Trigeminal/virologia , Células Vero , Proteínas do Envelope Viral/genéticaRESUMO
Rhesus macaques intrabronchially inoculated with simian varicella virus (SVV), the counterpart of human varicella-zoster virus (VZV), developed primary infection with viremia and rash, which resolved upon clearance of viremia, followed by the establishment of latency. To assess the role of CD4 T cell immunity in reactivation, monkeys were treated with a single 50-mg/kg dose of a humanized monoclonal anti-CD4 antibody; within 1 week, circulating CD4 T cells were reduced from 40 to 60% to 5 to 30% of the total T cell population and remained low for 2 months. Very low viremia was seen only in some of the treated monkeys. Zoster rash developed after 7 days in the monkey with the most extensive CD4 T cell depletion (5%) and in all other monkeys at 10 to 49 days posttreatment, with recurrent zoster in one treated monkey. SVV DNA was detected in the lung from two of five monkeys, in bronchial lymph nodes from one of the five monkeys, and in ganglia from at least two dermatomes in three of five monkeys. Immunofluorescence analysis of skin rash, lungs, lymph nodes, and ganglia revealed SVV ORF63 protein at the following sites: sweat glands in skin; type II cells in lung alveoli, macrophages, and dendritic cells in lymph nodes; and the neuronal cytoplasm of ganglia. Detection of SVV antigen in multiple tissues upon CD4 T cell depletion and virus reactivation suggests a critical role for CD4 T cell immunity in controlling varicella virus latency.IMPORTANCE Reactivation of latent VZV in humans can result in serious neurological complications. VZV-specific cell-mediated immunity is critical for the maintenance of latency. Similar to VZV in humans, SVV causes varicella in monkeys, establishes latency in ganglia, and reactivates to produce shingles. Here, we show that depletion of CD4 T cells in rhesus macaques results in SVV reactivation, with virus antigens found in zoster rash and SVV DNA and antigens found in lungs, lymph nodes, and ganglia. These results suggest the critical role of CD4 T cell immunity in controlling varicella virus latency.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Infecções por Herpesviridae/imunologia , Depleção Linfocítica , Pele/imunologia , Varicellovirus/isolamento & purificação , Ativação Viral/imunologia , Latência Viral/imunologia , Animais , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/virologia , Células Dendríticas/citologia , Células Dendríticas/imunologia , Células Dendríticas/virologia , Modelos Animais de Doenças , Feminino , Gânglios/citologia , Gânglios/imunologia , Gânglios/virologia , Infecções por Herpesviridae/patologia , Infecções por Herpesviridae/virologia , Pulmão/citologia , Pulmão/imunologia , Pulmão/virologia , Linfonodos/citologia , Linfonodos/imunologia , Linfonodos/virologia , Macaca mulatta , Masculino , Pele/citologia , Pele/virologiaRESUMO
Spiroplasma eriocheiris, a novel pathogen of Chinese mitten crab Eriocheir sinensis tremor disease, has led into catastrophic economic losses in aquaculture. S. eriocheiris invaded the hemocytes in the early stage, then invaded nerve tissue and caused typically paroxysmal tremors of pereiopod in the late stage of infection. The purpose of this study was to detect the infection mechanism of hemocytes in the early stage and thoracic ganglion in the late stage of S. eriocheiris infection at the protein level. Hemocytes and thoracic ganglion were collected at 24 h and 10 d after injection (the crabs with typical paroxysmal tremors of the pereiopod), respectively. TMT was performed with isobaric markers, followed by liquid chromatography tandem mass spectrometry (LC-MS/MS). In hemocytes, 127 proteins were up-regulated and 85 proteins were down-regulated in 2747 quantified proteins. Many proteins and process including proPO system proteins, hemolymph coagulation system proteins and lectins were differently expressed in hemocytes and involved in the early immune process of E. sinensis against S. eriocheiris infection. Meanwhile, 545 significantly different expression proteins (292 down-regulated and 253 up-regulated protein including a number of immune-associated, nervous system development and signal transmission related proteins) were identified in thoracic ganglion in the late stage of S. eriocheiris infection. The qRT-PCR analysis results shown that the selected significantly changed proteins in hemocytes and thoracic ganglion were consistent with the TMT proteomics. This paper reported for the first time to study the responses of crab hemocyte and thoracic ganglion against the S. eriocheiris infection at different stages. These findings help us understand the infection mechanism of S. eriocheiris at different stage with the different tissue.
Assuntos
Proteínas de Artrópodes/imunologia , Braquiúros/imunologia , Hemócitos/imunologia , Proteoma/imunologia , Spiroplasma/fisiologia , Animais , Braquiúros/microbiologia , Gânglios/imunologia , ProteômicaRESUMO
The enteric nervous system shares embryological, morphological, neurochemical, and functional features with the central nervous system. In addition to neurons and glia, the CNS includes a third component, microglia, which are functionally and immunophenotypically similar to macrophages, but a similar cell type has not previously been identified in enteric ganglia. In this study we identify a population of macrophages in the enteric ganglia, intermingling with the neurons and glia. These intraganglionic macrophages (IMs) are highly ramified and express the hematopoietic marker CD45, major histocompatibility complex (MHC) class II antigen, and chB6, a marker specific for B cells and microglia in avians. These IMs do not express antigens typically associated with T cells or dendritic cells. The CD45+ /ChB6+ /MHCII+ signature supports a hematopoietic origin and this was confirmed using intestinal chimeras in GFP-transgenic chick embryos. The presence of green fluorescent protein positive (GFP+) /CD45+ cells in the intestinal graft ENS confirms that IMs residing within enteric ganglia have a hematopoietic origin. IMs are also found in the ganglia of CSF1RGFP chicken and CX3CR1GFP mice. Based on the expression pattern and location of IMs in avians and rodents, we conclude that they represent a novel non-neural crest-derived microglia-like cell population within the enteric ganglia.
Assuntos
Sistema Nervoso Entérico/citologia , Sistema Nervoso Entérico/imunologia , Macrófagos/citologia , Macrófagos/imunologia , Animais , Embrião de Galinha , Gânglios/citologia , Gânglios/imunologia , Neuroimunomodulação/fisiologiaRESUMO
Neural-specific autoantibodies have been documented and their diagnostic utility validated in diseases affecting the neuraxis from cerebral cortex to the somatic, autonomic, and enteric nervous system and skeletal muscle. These neurological disorders occur both idiopathically and in a paraneoplastic context. Molecular identification of the antigens has expedited development of confirmatory and high-throughput tests for serum and cerebrospinal fluid, which permit early diagnosis and reveal the underlying molecular pathogenic mechanisms. The autoantibodies are classifiable on the basis of antigen location: intracellular (nuclear or cytoplasmic) or plasma membrane. Immunohistopathological studies of patients' biopsied and autopsied tissues suggest that effector T cells mediate the autoimmune neurological disorders for which defining autoantibodies recognize intracellular antigens. Antigens within intact cells are inaccessible to circulating antibody, and the associated neurological deficits rarely improve with antibody-depleting therapies. Tumoricidal therapies may arrest neurological progression, but symptom reversal is rare. In contrast, autoantibodies specific for plasma membrane antigens have pathogenic potential, and the associated neurological deficits are often amenable to antibody-depleting immunotherapy, such as plasma exchange and anti-B-cell monoclonal antibody therapy. These reversible neurological disorders are frequently misdiagnosed as neurodegenerative. The focus of this review is the immunobiology, pathophysiology, and clinical spectrum of autoimmune neurological disorders accompanied by neural-specific IgGs.
Assuntos
Autoantígenos/imunologia , Doenças Autoimunes do Sistema Nervoso/imunologia , Animais , Especificidade de Anticorpos/imunologia , Autoanticorpos/imunologia , Gânglios/imunologia , Humanos , Junção Neuromuscular/imunologia , Receptores de Neurotransmissores/imunologia , Membranas Sinápticas/imunologia , Transmissão Sináptica/imunologiaRESUMO
BACKGROUND: Acute gastroenteritis can precipitate irritable bowel syndrome (IBS) in humans. Cytolethal distending toxin is common to all pathogens causing gastroenteritis. Its active subunit, CdtB, is associated with post-infectious bowel changes in a rat model of Campylobacter jejuni infection, including small intestinal bacterial overgrowth (SIBO). AIM: To evaluate the role of host antibodies to CdtB in contributing to post-infectious functional sequelae in this rat model. METHODS: Ileal tissues from non-IBS human subjects, C. jejuni-infected and control rats were immunostained with antibodies to CdtB, c-Kit, S-100, PGP 9.5 and vinculin. Cytosolic and membrane proteins from mouse enteric neuronal cell lysates were immunoprecipitated with anti-CdtB and analyzed by mass spectrometry. ELISAs were performed on rat cardiac serum using CdtB or vinculin as antigens. RESULTS: Anti-CdtB antibodies bound to a cytosolic protein in interstitial cells of Cajal (ICC) and myenteric ganglia in C. jejuni-infected and naïve rats and human subjects. Mass spectrometry identified vinculin, confirmed by co-localization and ELISAs. Anti-CdtB antibodies were higher in C. jejuni-infected rats (1.27 ± 0.15) than controls (1.76 ± 0.12) (P < 0.05), and rats that developed SIBO (2.01 ± 0.18) vs. rats that did not (1.44 ± 0.11) (P = 0.019). Vinculin expression levels were reduced in C. jejuni-infected rats (0.058 ± 0.053) versus controls (0.087 ± 0.023) (P = 0.0001), with greater reductions in rats with two C. jejuni infections (P = 0.0001) and rats that developed SIBO (P = 0.001). CONCLUSIONS: Host anti-CdtB antibodies cross-react with vinculin in ICC and myenteric ganglia, required for normal gut motility. Circulating antibody levels and loss of vinculin expression correlate with number of C. jejuni exposures and SIBO, suggesting that effects on vinculin are important in the effects of C. jejuni infection on the host gut.
Assuntos
Anticorpos Antibacterianos/imunologia , Autoimunidade , Toxinas Bacterianas/imunologia , Infecções por Campylobacter/imunologia , Campylobacter jejuni/imunologia , Enterite/imunologia , Intestino Delgado/imunologia , Vinculina/imunologia , Animais , Infecções por Campylobacter/microbiologia , Infecções por Campylobacter/fisiopatologia , Campylobacter jejuni/patogenicidade , Reações Cruzadas , Modelos Animais de Doenças , Sistema Nervoso Entérico/imunologia , Sistema Nervoso Entérico/microbiologia , Enterite/microbiologia , Enterite/fisiopatologia , Gânglios/imunologia , Gânglios/microbiologia , Humanos , Células Intersticiais de Cajal/imunologia , Células Intersticiais de Cajal/microbiologia , Intestino Delgado/inervação , Intestino Delgado/microbiologia , Intestino Delgado/fisiopatologia , Camundongos , Fenótipo , RatosRESUMO
The caudal mesenteric ganglion (CaMG) is a prevetrebral ganglion which provides innervation to a number of organs in the abdominal and pelvic cavity. The morphology of CaMG and the chemical coding of neurones in this ganglion have been described in humans and many animal species, but data on this topic in the sheep are entirely lacking. This prompted us to undertake a study to determine the localization and morphology of sheep CaMG as well as immunohistochemical properties of its neurons. The study was carried out on 8 adult sheep, weighing from 40 to 60 kg each. The sheep were deeply anaesthetised and transcardially perfused with 4% paraformaldehyde. CaMG-s were exposed and their location was determined. Macroanatomical observations have revealed that the ovine CaMG is located at the level of last two lumbar (L5 or L6) and the first sacral (S1) vertebrae. The ganglion represents an unpaired structure composed of several, sequentially arranged aggregates of neurons. Immunohistochemical investigations revealed that nearly all (99.5%) the neurons were DßH-IR and were richly supplied by VACHT-IR nerve terminals forming "basket-like" structures around the perikarya. VACHT-IR neurones were not determined. Many neurons (55%) contained immunoreactivity to NPY, some of them (10%) stained for Met-ENK and solitary nerve cells were GAL-positive. CGRP-IR nerve fibres were numerous and a large number of them simultaneously expressed immunoreactivity to SP. Single, weakly stained neurones were SP-IR and only very few nerve cells weakly stained for VIP.
Assuntos
Gânglios/anatomia & histologia , Gânglios/imunologia , Imuno-Histoquímica/veterinária , Mesentério/inervação , Ovinos/anatomia & histologia , Animais , Gânglios/metabolismo , Ovinos/metabolismoRESUMO
Ganglia of monkeys with reactivated simian varicella virus (SVV) contained more CD8 than CD4 T cells around neurons. The abundance of CD8 T cells was greater less than 2 months after reactivation than that at later times and correlated with that of CXCL10 RNA but not with those of SVV protein or open reading frame 61 (ORF61) antisense RNA. CXCL10 RNA colocalized with T-cell clusters. After SVV reactivation, transient T-cell infiltration, possibly mediated by CXCL10, parallels varicella zoster virus (VZV) reactivation in humans.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Quimiocina CXCL10/metabolismo , Gânglios/imunologia , Infecções por Herpesviridae/imunologia , Infecções por Herpesviridae/virologia , Neurônios/imunologia , Varicellovirus/imunologia , Varicellovirus/metabolismo , Varicellovirus/fisiologia , Animais , Linfócitos T CD8-Positivos/metabolismo , DNA Viral/genética , Gânglios/metabolismo , Gânglios/virologia , Infecções por Herpesviridae/genética , Macaca fascicularis , Neurônios/virologia , Fases de Leitura Aberta , RNA Antissenso/biossíntese , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Varicellovirus/genética , Carga Viral , Ativação Viral , Latência Viral/genéticaRESUMO
Varicella-zoster virus (VZV) causes varicella (chickenpox), becomes latent in ganglia along the entire neuraxis, and may reactivate to cause herpes zoster (shingles). VZV may infect ganglia via retrograde axonal transport from infected skin or through hematogenous spread. Simian varicella virus (SVV) infection of rhesus macaques provides a useful model system to study the pathogenesis of human VZV infection. To dissect the virus and host immune factors during acute SVV infection, we analyzed four SVV-seronegative Chinese rhesus macaques infected intratracheally with cell-associated 5 × 10³ plaque-forming units (pfu) of SVV-expressing green fluorescent protein (n = 2) or 5 × 104 pfu of wild-type SVV (n = 2). All monkeys developed viremia and SVV-specific adaptive B- and T-cell immune responses, but none developed skin rash. At necropsy 21 days postinfection, SVV DNA was found in ganglia along the entire neuraxis and in viscera, and SVV RNA was found in ganglia, but not in viscera. The amount of SVV inoculum was associated with the extent of viremia and the immune response to virus. Our findings demonstrate that acute SVV infection of Chinese rhesus macaques leads to ganglionic infection by the hematogenous route and the induction of a virus-specific adaptive memory response in the absence of skin rash.
Assuntos
Varicela/virologia , Gânglios/virologia , Herpesvirus Humano 3/fisiologia , Viremia/virologia , Imunidade Adaptativa , Animais , Linfócitos B/imunologia , Linfócitos B/virologia , Varicela/imunologia , Varicela/patologia , DNA Viral/biossíntese , Modelos Animais de Doenças , Exantema , Gânglios/imunologia , Gânglios/patologia , Humanos , Macaca mulatta , Pele/virologia , Linfócitos T/imunologia , Linfócitos T/virologia , Viremia/imunologia , Viremia/patologia , Latência ViralRESUMO
Varicella-zoster virus (VZV) causes varicella (chicken pox) and establishes latency in ganglia, from where it reactivates to cause herpes zoster (shingles), which is often followed by postherpetic neuralgia (PHN), causing severe neuropathic pain that can last for years after the rash. Despite the major impact of herpes zoster and PHN on quality of life, the nature and kinetics of the virus-immune cell interactions that result in ganglion damage have not been defined. We obtained rare material consisting of seven sensory ganglia from three donors who had suffered from herpes zoster between 1 and 4.5 months before death but who had not died from herpes zoster. We performed immunostaining to investigate the site of VZV infection and to phenotype immune cells in these ganglia. VZV antigen was localized almost exclusively to neurons, and in at least one case it persisted long after resolution of the rash. The large immune infiltrate consisted of noncytolytic CD8(+) T cells, with lesser numbers of CD4(+) T cells, B cells, NK cells, and macrophages and no dendritic cells. VZV antigen-positive neurons did not express detectable major histocompatibility complex (MHC) class I, nor did CD8(+) T cells surround infected neurons, suggesting that mechanisms of immune control may not be dependent on direct contact. This is the first report defining the nature of the immune response in ganglia following herpes zoster and provides evidence for persistence of non-latency-associated viral antigen and inflammation beyond rash resolution.
Assuntos
Gânglios/imunologia , Herpes Zoster/complicações , Herpesvirus Humano 3/fisiologia , Neuralgia Pós-Herpética/imunologia , Adolescente , Adulto , Idoso de 80 Anos ou mais , Feminino , Gânglios/virologia , Herpes Zoster/imunologia , Herpes Zoster/virologia , Herpesvirus Humano 3/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Neuralgia Pós-Herpética/etiologia , Neuralgia Pós-Herpética/virologia , Neurônios/imunologia , Neurônios/virologiaRESUMO
Haematopoietic immune cell populations play an important role in the pathogenesis of numerous neurological disorders. To better understand the function of resident mononuclear phagocytes and migrating leukocytes in the central nervous system (CNS), the definition of these populations in healthy individuals is crucial. Therefore, the composition of CNS-associated leukocytes, isolated from macaque brain tissue, was assessed using multicolor flow cytometry. We established a combination of antibodies directed against nine different antigens that enabled a precise classification of all major immune cell populations in a single tube. Macrophages, dendritic cells (DCs), B and T lymphocytes, and natural killer (NK) cells were differentiated in CNS and peripheral blood. Additionally, microglia cells were detected in the brain. Using this antibody combination also allowed the discrimination of functionally different subsets among the distinct immunocyte populations, for example, CD8 positive cytotoxic T lymphocytes. About 95% of the leukocytes in the brain are microglia cells. Two additional myeloid cell populations, CD14 positive macrophages and CD11c-positive DCs, were also identified. In contrast to blood, where macrophages are more abundant, DCs outnumbered macrophages in the brain. Among lymphocytes, proportions of CD20 positive B lymphocytes were decreased, and T lymphocytes as well as NK cells were increased in brain compared to blood. Significant changes were also detected for macrophage and T-cell subpopulations. The nonexclusive expression of certain surface makers on different cell populations demanded a simultaneous classification of all intrathecal immune cells. Knowing their exact composition offers new insights on interaction and regulation in inflammatory processes and will be instrumental to monitor alterations in the course of neurological diseases.
Assuntos
Subpopulações de Linfócitos B/citologia , Encéfalo/citologia , Células Dendríticas/citologia , Citometria de Fluxo/métodos , Gânglios/citologia , Células Matadoras Naturais/citologia , Macrófagos/citologia , Subpopulações de Linfócitos T/citologia , Animais , Antígenos CD , Subpopulações de Linfócitos B/imunologia , Encéfalo/imunologia , Diferenciação Celular , Células Dendríticas/imunologia , Feminino , Gânglios/imunologia , Células Matadoras Naturais/imunologia , Contagem de Linfócitos , Macaca , Macrófagos/imunologia , Masculino , Subpopulações de Linfócitos T/imunologiaRESUMO
Herpes simplex virus type 1 (HSV-1) is a prevalent human pathogen. HSV-1 genomes persist in trigeminal ganglia neuronal nuclei as chromatinized episomes, while epithelial cells are typically killed by lytic infection. Fluctuations in anti-viral responses, broadly defined, may underlay periodic reactivations. The ganglionic immune response to HSV-1 infection includes cell-intrinsic responses in neurons, innate sensing by several cell types, and the infiltration and persistence of antigen-specific T-cells. The mechanisms specifying the contrasting fates of HSV-1 in neurons and epithelial cells may include differential genome silencing and chromatinization, dictated by variation in access of immune modulating viral tegument proteins to the cell body, and protection of neurons by autophagy. Innate responses have the capacity of recruiting additional immune cells and paracrine activity on parenchymal cells, for example via chemokines and type I interferons. In both mice and humans, HSV-1-specific CD8 and CD4 T-cells are recruited to ganglia, with mechanistic studies suggesting active roles in immune surveillance and control of reactivation. In this review we focus mainly on HSV-1 and the TG, comparing and contrasting where possible observational, interventional, and in vitro studies between humans and animal hosts.
Assuntos
Gânglios/imunologia , Herpes Simples/imunologia , Herpesvirus Humano 1/imunologia , Imunidade , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Modelos Animais de Doenças , Herpes Simples/virologia , Herpesvirus Humano 1/genética , Humanos , Camundongos , Gânglio Trigeminal/virologia , Latência ViralRESUMO
The presence and pattern of pituitary adenylate cyclase activating polypeptide (PACAP) type I (PAC1) receptors were identified by means of pre- and post-embedding immunocytochemical methods in the ventral nerve cord ganglia (VNC) of the earthworm Eisenia fetida. Light and electron microscopic observations revealed the exact anatomical positions of labeled structures suggesting that PACAP mediates the activity of some interneurons, a few small motoneurons and certain sensory fibers that are located in ventrolateral, ventromedial and intermediomedial sensory longitudinal axon bundles of the VNC ganglia. No labeling was located on large interneuronal systems such as dorsal medial and lateral giant axon systems and ventral giant axons. At the ultrastructural level labeling was mainly restricted to endo- and plasma membranes showing characteristic unequal distribution in various neuron parts. An increasing abundance of PAC1 receptors located on both rough endoplasmic reticulum and plasma membranes was seen from perikarya to neural processes, indicating that intracellular membrane traffic might play a crucial role in the transportation of PAC1 receptors. High number of PAC1 receptors was found in both pre- and postsynaptic membranes in addition to extrasynaptic sites suggesting that PACAP acts as neurotransmitter and neuromodulator in the earthworm nervous system.
Assuntos
Gânglios/metabolismo , Gânglios/ultraestrutura , Modelos Neurológicos , Oligoquetos/metabolismo , Oligoquetos/ultraestrutura , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Animais , Gânglios/imunologia , Imuno-Histoquímica , Microscopia Imunoeletrônica , Oligoquetos/imunologiaRESUMO
OBJECTIVE: To investigate whether copolymer-1 (Cop-1), a synthesized analogue of myelin basic protein, can protect the retina ganglion cells (RGCs) and possible mechanism thereof. METHODS: Vortex veins of rats were ligated to induce an increase of intraocular pressure (IOP) so as to establish glaucoma models. 106 rat models were randomly divided into 2 equal groups: Cop-1 Group undergoing subcutaneous injection of 200 microg Cop-1, and phosphate buffered solution (PBS) Group undergoing PBS injection as controls. Fluorogold was used to retrogradely label the RGCs. 10, 17, 24, and 31 days after the immunization some rats were killed with their eyeballs taken out. The fluorogold positive spots were calculated. Anti-rat T cell receptor (TCR) monoclonal antibody was used to mark T cells in the retina. RESULTS: 17, 24, and 31 days after the immunization, the RGC density of the Cop-1 Group were (2617 +/- 17)/mm(2), (2588 +/- 206)/mm(2), and (2394 +/- 15)/mm(2) respectively, all significantly higher than those of the PBS Group [(2357 +/- 37)/mm(2), (2277 +/- 340)/mm(2), and (2129 +/- 17)/mm(2) respectively, all P < 0.05]. 10, 17, 24, and 31 days after the immunization the numbers of T cells in the retina of Cop-1 Group were (11.3 +/- 2.8)/mm(2), (36.7 +/- 5.2)/mm(2), (33.9 +/- 3.0)/mm(2), and (21.4 +/- 5.9)/mm(2), all significantly higher than those of PBS Group (4.7 +/- 3.6)/mm(2), (19.7 +/- 2.4)/mm(2), (15.3 +/- 4.0)/mm(2), and (13.3 +/- 4.4)/mm(2) respectively, all P < 0.01). CONCLUSION: Cop-1 protects RGCs. The injury of RGCs induced by increased IOP results in congregation of T cells. Cop-1 increases the number of T-lymphocyte cells congregating in the retina, which may be related to its neuroprotection.
Assuntos
Hipertensão Ocular/prevenção & controle , Nervo Óptico/efeitos dos fármacos , Peptídeos/farmacologia , Animais , Autoimunidade/efeitos dos fármacos , Modelos Animais de Doenças , Gânglios/citologia , Gânglios/efeitos dos fármacos , Gânglios/imunologia , Acetato de Glatiramer , Glaucoma/imunologia , Glaucoma/patologia , Glaucoma/prevenção & controle , Imunossupressores/farmacologia , Contagem de Linfócitos , Masculino , Hipertensão Ocular/fisiopatologia , Nervo Óptico/imunologia , Nervo Óptico/fisiopatologia , Ratos , Ratos Sprague-Dawley , Retina/citologia , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologiaRESUMO
Recent studies, including our own, have accumulated evidence suggesting the etiological participation of varicella-zoster virus in multiple sclerosis. If confirmed, complex issues of individual susceptibility and immunopathogenesis would have to be unveiled.
Assuntos
Varicela/complicações , Varicela/imunologia , Herpes Zoster/imunologia , Herpes Zoster/virologia , Herpesvirus Humano 3/imunologia , Esclerose Múltipla/imunologia , Esclerose Múltipla/virologia , Varicela/fisiopatologia , Gânglios/imunologia , Gânglios/virologia , Predisposição Genética para Doença/genética , Herpes Zoster/fisiopatologia , Herpesvirus Humano 3/genética , Humanos , Esclerose Múltipla/fisiopatologia , Esclerose Múltipla Recidivante-Remitente/imunologia , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Esclerose Múltipla Recidivante-Remitente/virologia , Vacinas/imunologia , Vacinas/uso terapêutico , Carga ViralRESUMO
In recent years, incidence of autoimmune encephalopathies has increased. The diagnosis of the severe form of autoimmune encephalopathy is not difficult; however, milder forms can be misdiagnosed as general encephalopathies. We often treat Hashimoto's encephalopathy, which has diverse clinical symptoms and is often misdiagnosed as a psychosomatic disease. We have found that the neurological findings and symptoms of patients with Hashimoto's encephalopathy are similar to those of psychogenic diseases, such as giveway weakness and atypical sensory disorder. To understand the mechanism underlying these symptoms, we propose a new concept: neurological symptoms of diffuse brain damage. This theory is based on the premise that etiologically, symptoms observed were caused by diffuse, spotty, and shaded brain damage due to autoimmune encephalopathies. We also found similar neurological conditions in patients with anti-ganglionic acetylcholine receptor antibody-related encephalopathy, encephalopathies that developed after injection of the cervical cancer vaccine, and encephalopathies associated with Stiff person syndrome. In conclusion, the clinical features of autoimmune encephalopathy include the "neurological symptoms of diffuse brain damage" as well as the presence of antibodies. We could diagnose autoimmune encephalopathy more easily, using this new diagnostic concept.
Assuntos
Encefalopatias/diagnóstico , Diagnóstico Diferencial , Doenças do Sistema Imunitário/complicações , Encefalopatias/imunologia , Gânglios/imunologia , Humanos , PrognósticoAssuntos
Alphaherpesvirinae , Gânglios/metabolismo , Infecções por Herpesviridae , Neurônios/metabolismo , Latência Viral , Alphaherpesvirinae/genética , Alphaherpesvirinae/imunologia , Alphaherpesvirinae/metabolismo , Animais , Colorado , Gânglios/imunologia , Gânglios/patologia , Gânglios/virologia , Regulação Viral da Expressão Gênica , Genoma Viral , Infecções por Herpesviridae/imunologia , Infecções por Herpesviridae/metabolismo , Infecções por Herpesviridae/patologia , Infecções por Herpesviridae/virologia , Humanos , Macaca mulatta , Camundongos , MicroRNAs/metabolismo , Neurônios/patologia , Filogenia , Ratos , Ativação Viral/genética , Ativação Viral/imunologia , Latência Viral/genética , Latência Viral/imunologia , Replicação Viral/genética , Replicação Viral/imunologiaRESUMO
An isolate of Nipah virus was injected into fertile eggs via the allantoic cavity or yolk sac. Allantoic inoculation resulted in considerable pathological variation and only partial mortality. Dead embryos showed severe necrosis in the brain and congestion in the kidney and the subcutis of limbs. In contrast, yolk sac inoculation led to uniform infection and mortality, the dead embryos exhibiting the same lesions as those described above but without the subcutaneous congestion. Histological lesions in dead embryos inoculated by either route were similar and particularly severe in the central nervous system. Viral antigens were detected mainly in the vasculature and neurons. The results indicated that Nipah virus is highly pathogenic to chicken embryos, and that the route of inoculation is an important determinant of the course of disease. The findings also suggested that yolk sac inoculation can be used for viral titration, and that the chicken embryo represents a useful model for studying the vascular and neuronal tropisms of Nipah virus.
Assuntos
Antígenos Virais/metabolismo , Infecções por Henipavirus/patologia , Vírus Nipah/patogenicidade , Animais , Antígenos Virais/genética , Encéfalo/imunologia , Encéfalo/patologia , Encéfalo/virologia , Embrião de Galinha , Modelos Animais de Doenças , Suscetibilidade a Doenças/virologia , Endotélio Vascular/imunologia , Endotélio Vascular/patologia , Endotélio Vascular/virologia , Gânglios/imunologia , Gânglios/patologia , Gânglios/virologia , Regulação Viral da Expressão Gênica , Coração/virologia , Infecções por Henipavirus/imunologia , Imuno-Histoquímica , Rim/imunologia , Rim/patologia , Rim/virologia , Miocárdio/imunologia , Miocárdio/patologia , Vírus Nipah/imunologia , Saco Vitelino/virologiaRESUMO
Previous studies have found a few intralingual ganglionic cells that were immunoreactive to vasoactive intestinal polypeptide (VIP) in the frog. A recent study reported a large number of such cells, and the possibility of the release of substance P (SP) from these. The aim of the present study was to investigate the distribution, origin, and colocalization of VIP- and SP- immunoreactive nerves in the tongue of the bullfrog, R. catesbeiana. In addition, the study also examined the colocalization of SP and phospholipase Cß2 (PLCß2 ) in the tongue and jugular ganglion. VIP immunoreactivity was seen in unipolar cells that were sparse in nerve bundles in the submucosal and muscle layers. The density of VIP-immunoreactive cells was approximately 4.8 cells/mm(3) . Their fibers terminated in the vicinity of the epithelial basal layer of the fungiform papillae. SP immunoreactivity was not seen in the VIP-immunoreactive cells, but was observed in pseudounipolar cells in the jugular ganglion. The SP fibers terminated close to the free surface, showing spindle- and button-like profiles. Transection of glossopharyngeal nerve resulted in the persistence of VIP-immunoreactive cells and the disappearance of SP-immunoreactive fibers in the tongue. SP immunoreactivity was co-expressed with PLCß2 in both the tongue and jugular ganglia. No PLCß2 immunoreactivity was seen in cells comprising the epithelial taste disk. These findings indicate that the origin of VIP nerve fibers are unipolar cells in the tongue, and SP and PLCß2 fibers originate from pseudounipolar cells that may be able to release SP primarily in the jugular ganglion. Anat Rec, 299:929-942, 2016. © 2016 Wiley Periodicals, Inc.