RESUMEN
BACKGROUND: Listeria monocytogenes (Lm) is a bacterial pathogen of major concern for humans and ruminants due to its neuroinvasive potential and its ability to cause deadly encephalitis (neurolisteriosis). On one hand, polymorphonuclear neutrophils (PMN) are key players in the defense against Lm, but on the other hand intracerebral infiltration with PMN is associated with significant neural tissue damage. Lm-PMN interactions in neurolisteriosis are poorly investigated, and factors inducing PMN chemotaxis to infectious foci containing Lm in the central nervous system (CNS) remain unidentified. METHODS: In this study, we assessed bovine PMN chemotaxis towards Lm and supernatants of infected endogenous brain cell populations in ex vivo chemotaxis assays, to identify chemotactic stimuli for PMN chemotaxis towards Lm in the brain. In addition, microglial secretion of IL-8 was assessed both ex vivo and in situ. RESULTS: Our data show that neither Lm cell wall components nor intact bacteria elicit chemotaxis of bovine PMN ex vivo. Moreover, astrocytes and neural cells fail to induce bovine PMN chemotaxis upon infection. In contrast, supernatant from Lm infected microglia readily induced chemotaxis of bovine PMN. Microglial expression and secretion of IL-8 was identified during early Lm infection in vitro and in situ, although IL-8 blocking with a specific antibody could not abrogate PMN chemotaxis towards Lm infected microglial supernatant. CONCLUSIONS: These data provide evidence that host-derived rather than bacterial factors trigger PMN chemotaxis to bacterial foci in the CNS, that microglia have a primary role as initiators of bovine PMN chemotaxis into the brain during neurolisteriosis and that blockade of these factors could be a therapeutic target to limit intrathecal PMN chemotaxis and PMN associated damage in neurolisteriosis.
Asunto(s)
Listeria monocytogenes , Humanos , Animales , Bovinos , Microglía , Neutrófilos/metabolismo , Quimiotaxis , Interleucina-8/metabolismo , Quimiotaxis de LeucocitoRESUMEN
Choroid plexus tumors (CPT) are intraventricular neoplasms accounting for 10% of all primary central nervous system tumors in dogs. They are frequently classified according to the human WHO classification into choroid plexus papilloma (CPP, grade I), atypical CPP (aCPP, grade II), and choroid plexus carcinoma (CPC, grade III). Histological features observed in canine CPT such as increased vascular density (IVD) and glomeruloid microvascular proliferation (GMVP) are not part of the WHO classification. This multi-centric study aimed to investigate tumor-associated vascular hyperplasia in dogs by determining the prevalence of GMVP and IVD in 52 canine CPT and their association with tumor grade. In addition, the expression of angiogenic factors was assessed by immunohistochemistry in 25 tumors to investigate the pathogenesis of tumor-associated vascular hyperplasia. Based on the classical histological hallmarks, this study of 52 CPT identified 22 (42%) CPP (grade I) and 30 of (58%) CPC (grade III). GMVP was more prevalent in CPC (13/30; 43%) than CPP (1/22; 4%), whereas IVD occurred to a similar extent in CPP and CPC. Desmoplasia was more common in CPC (19/30; 63%) than CPP (2/22; 9%), and similarly, the proliferative index (PI) of neoplastic epithelium was significantly higher in CPC (5.14%) than CPP (0.94%). The majority of CPT expressed platelet-derived growth factor (PDGF), PDGFRα, PDGFRß, and vascular endothelial growth factor (VEGF) irrespective of tumor grade or tumor-associated vascular hyperplasia. These results suggest that tumor-associated GMVP, desmoplasia, and PI may serve as histological indicators of malignancy in CPT.
Asunto(s)
Carcinoma/veterinaria , Neoplasias del Plexo Coroideo/veterinaria , Enfermedades de los Perros/patología , Neovascularización Patológica/veterinaria , Animales , Carcinoma/irrigación sanguínea , Carcinoma/patología , Neoplasias del Plexo Coroideo/irrigación sanguínea , Neoplasias del Plexo Coroideo/patología , Perros , Neovascularización Patológica/patología , Estudios RetrospectivosRESUMEN
A case of diffuse leptomeningeal oligodendrogliomatosis affecting the brain and spinal cord of a dog is presented. A 7.5-year old, male neutered Staffordshire bull terrier presented for evaluation of a chronic history of tetraparesis and seizures, with a multifocal neuroanatomical localization was determined. Extra-axial intradural lesions with an atypical presentation of a dural tail sign were seen on MRI. Histologically, the lesions were consistent with leptomeningeal oligodendrogliomatosis. To the authors' knowledge, a dural tail sign has not previously been reported as an MRI characteristic of diffuse leptomeningeal oligodendrogliomatosis in dogs.
Asunto(s)
Encéfalo/diagnóstico por imagen , Enfermedades de los Perros/diagnóstico por imagen , Imagen por Resonancia Magnética/veterinaria , Neoplasias Meníngeas/veterinaria , Oligodendroglioma/veterinaria , Médula Espinal/diagnóstico por imagen , Animales , Encéfalo/patología , Enfermedades de los Perros/patología , Perros , Masculino , Neoplasias Meníngeas/diagnóstico por imagen , Neoplasias Meníngeas/patología , Oligodendroglioma/diagnóstico por imagen , Oligodendroglioma/patología , Médula Espinal/patologíaRESUMEN
Three different types of bovine spongiform encephalopathy (BSE) are known and supposedly caused by distinct prion strains: the classical (C-) BSE type that was typically found during the BSE epidemic, and two relatively rare atypical BSE types, termed H-BSE and L-BSE. The three BSE types differ in the molecular phenotype of the disease associated prion protein, namely the N-terminally truncated proteinase K (PK) resistant prion protein fragment (PrPres). In this study, we report and analyze yet another PrPres type (PrPres-2011), which was found in severely autolytic brain samples of two cows in the framework of disease surveillance in Switzerland in 2011. Analysis of brain tissues from these animals by PK titration and PK inhibitor assays ruled out the process of autolysis as the cause for the aberrant PrPres profile. Immunochemical characterization of the PrP fragments present in the 2011 cases by epitope mapping indicated that PrPres-2011 corresponds in its primary sequence to the physiologically occurring PrP-C1 fragment. However, high speed centrifugation, sucrose gradient assay and NaPTA precipitation revealed biochemical similarities between PrPres-2011 and the disease-associated prion protein found in BSE affected cattle in terms of detergent insolubility, PK resistance and PrP aggregation. Although it remains to be established whether PrPres-2011 is associated with a transmissible disease, our results point out the need of further research on the role the PrP-C1 aggregation and misfolding in health and disease.
Asunto(s)
Tronco Encefálico/química , Encefalopatía Espongiforme Bovina/metabolismo , Fragmentos de Péptidos/análisis , Proteínas PrPSc/agonistas , Envejecimiento/metabolismo , Animales , Autólisis , Western Blotting , Tronco Encefálico/metabolismo , Bovinos , Detergentes/química , Encefalopatía Espongiforme Bovina/genética , Mapeo Epitopo , Fragmentos de Péptidos/química , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/metabolismo , Proteínas PrPSc/química , Proteínas PrPSc/genética , Proteínas PrPSc/metabolismo , Agregado de Proteínas , Solubilidad , Suiza , UltracentrifugaciónRESUMEN
Toll-like receptor (TLR)-dependent pathways control the activation of various immune cells and the production of cytokines and chemokines that are important in innate immune control of viruses, including mouse cytomegalovirus (MCMV). Here we report that upon MCMV infection wild-type and TLR7(-/-) male mice were more resistant than their female counterparts, while TLR9(-/-) male and female mice showed similar susceptibility. Interestingly, 36 h upon MCMV infection TLR9 mRNA expression was higher in male than in female mouse spleens. MCMV infection led to stronger reduction of marginal zone (MZ) B cells, and higher infiltration of plasmacytoid dendritic cells and neutrophils in wild-type male than female mice, while no such sex differences were observed in TLR9(-/-) mice. In accordance, the serum levels of KC and MIP-2, major neutrophil chemoattractants, were higher in wild-type, but not in TLR9(-/-), male versus female mice. Wild-type MCMV-infected female mice showed more severe liver inflammation, necrosis and steatosis compared to infected male mice. Our data demonstrate sex differences in susceptibility to MCMV infection, accompanied by a lower activation of the innate immune system in female mice, and can be attributed, at least in a certain degree, to the lower expression of TLR9 in female than male mice.
Asunto(s)
Infecciones por Citomegalovirus/genética , Inmunidad Innata , Glicoproteínas de Membrana/genética , Muromegalovirus/inmunología , Receptor Toll-Like 7/genética , Receptor Toll-Like 9/genética , Animales , Linfocitos B/inmunología , Linfocitos B/virología , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/virología , Células Dendríticas/inmunología , Células Dendríticas/virología , Susceptibilidad a Enfermedades , Femenino , Regulación de la Expresión Génica , Interacciones Huésped-Patógeno , Hígado/patología , Hígado/virología , Masculino , Glicoproteínas de Membrana/deficiencia , Glicoproteínas de Membrana/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Neutrófilos/inmunología , Neutrófilos/virología , ARN Mensajero/biosíntesis , Factores Sexuales , Bazo/patología , Bazo/virología , Receptor Toll-Like 7/deficiencia , Receptor Toll-Like 7/inmunología , Receptor Toll-Like 9/deficiencia , Receptor Toll-Like 9/inmunologíaRESUMEN
An 11-year-old male, neutered European cat was presented for anisocoria due to pupillary dilation in the right eye. Ophthalmic findings were restricted to this eye and consisted of a raised, darkly pigmented, retrolental mass associated with retinal detachment. Ultrasonography identified the mass lesion protruding into the vitreous cavity from the posterior pole of the eyeball and confirmed the detachment of the retina. A tentative diagnosis of an intraocular tumor was made. Radiographic evaluation and retromandibular lymph node cytology did not reveal evidence of distant metastasis. Orbital exenteration of the affected eye was performed and the tumor was diagnosed as a choroidal melanocytic tumor with no criteria of malignancy (melanocytoma). The cat died 5 months later from renal lymphoma, and necropsy did not detect metastasis of the melanocytic tumor. To our knowledge this is the first reported case of feline choroidal melanocytoma.