RESUMO
BACKGROUND: It is assumed that moderate exercise may improve resistance to infection and reduce inflammation, but there are limited data to support this assumption in an infection model. METHODS: BALB/cJ mice were assigned to the following groups: no exercise (NON-EX), 1 session of acute exercise (A-EX), or chronic exercise for approximately 3.5 months (C-EX). Mice were infected with influenza (C-EX mice infected at rest; A-EX mice infected 15 min after exercise). RESULTS: C-EX mice demonstrated the lowest severity of infection, assessed by body weight loss and food intake. There was less virus in the lungs at day 5 after infection in C-EX and A-EX mice compared with NON-EX mice (P = .02) and less virus at day 2 after infection only in C-EX mice (P = .07). Soon after infection (day 2), interleukin 6 (IL-6), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1beta, and tumor necrosis factor alpha in the bronchoalveolar lavage (BAL) fluid were lower in C-EX and A-EX than in NON-EX mice. At day 5 after infection, the BAL fluid from C-EX (but not A-EX) mice had less IL-6, interleukin 12p40, granulocyte colony-stimulating factor, keratinococyte-derived chemokine, and MCP-1 than that from NON-EX mice. A trend toward reduced immunopathologic response was found in C-EX mice. CONCLUSIONS: Chronic exercise resulted in reduced symptoms, virus load, and levels of inflammatory cytokine and chemokines. Acute exercise also showed some benefit, which was limited to the early phase of infection.
Assuntos
Terapia por Exercício/métodos , Vírus da Influenza A , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Animais , Líquido da Lavagem Broncoalveolar/imunologia , Quimiocinas/análise , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/fisiopatologia , Aptidão Física , Índice de Gravidade de Doença , Carga ViralRESUMO
A distinct strain of scrapie identified in sheep of Norway in 1998 has since been identified in numerous countries throughout Europe. The disease is known as Nor98 or Nor98-like scrapie, among other names. Distinctions between classic scrapie and Nor98 scrapie are made based on histopathology and immunodiagnostic results. There are also differences in the epidemiology, typical signalment, and likelihood of clinical signs being observed. In addition, sheep that have genotypes associated with resistance to classic scrapie are not spared from Nor98 disease. The various differences between classic and Nor98 scrapie have been consistently reported in the vast majority of cases described across Europe. The current study describes in detail the pathologic changes and diagnostic results of the first 6 cases of Nor98 scrapie disease diagnosed in sheep of the United States.
Assuntos
Príons/genética , Scrapie/diagnóstico , Animais , Encéfalo/patologia , Feminino , Masculino , Scrapie/epidemiologia , Scrapie/genética , Ovinos , Coloração e Rotulagem , Estados Unidos/epidemiologiaRESUMO
Activation of the transcription factor Stat1 by interferon-gamma (IFN-gamma) is an important step in the development of antimicrobial effector mechanisms against many bacterial pathogens. Susceptibility to murine Lyme arthritis has been correlated with the production of several proinflammatory cytokines, especially IFN-gamma. To determine the role of IFN-mediated effector mechanisms in the development of Lyme borreliosis, we infected Stat1-deficient mice on both resistant (DBA), and susceptible (C3H) genetic backgrounds. Arthritis in Stat1(/) mice was similar to that of wild-type controls in both mouse strains. Spirochete loads in tissues were also unchanged in Stat1(/) mice. C3H Stat1(/) mice exhibited increased inflammation in the heart, whereas carditis was unchanged in DBA Stat1(/) mice. These results demonstrate that inhibition of macrophage activation and responses to IFN-gamma-mediated signaling do not alter the arthritis resistance or susceptibility phenotype; however, they do affect the severity of carditis in susceptible mouse strains.
Assuntos
Artrite/patologia , Grupo Borrelia Burgdorferi/patogenicidade , Doença de Lyme/genética , Miocardite/microbiologia , Miocardite/patologia , Fator de Transcrição STAT1/deficiência , Animais , Cruzamentos Genéticos , Doença de Lyme/imunologia , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos DBA , Camundongos Endogâmicos , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/imunologiaRESUMO
A cell model of primary monocytes and other mononuclear cells isolated from equine blood was used to study the kinetics of West Nile virus (WNV) replication in a natural host. West Nile virus has emerged on the North American continent as a significant cause of morbidity and mortality in a wide range of avian and mammalian species. While other flaviviruses are known to infect monocytes and lymphocytes, the ability of WNV to productively replicate in specific immune cells of peripheral blood has not been assessed. In this study, enriched populations of monocytes and lymphocytes as well as purified monocytes, CD4+, CD8+ and B lymphocytes were obtained from equine blood. Productive WNV replication was demonstrated by viral growth curves, quantitative RT-PCR for WNV RNA, and indirect immunofluorescence detection of a non-structural WNV protein. Enriched and purified monocytes consistently supported productive viral replication in blood from nine of nine horses tested while a minor subset of CD4+ lymphocytes supported productive replication in cells from three of the nine horses tested. Peak viral titers of 3.2-6.6 log10 PFU/ml were reached at 6 days post-inoculation (p.i.) and titers were maintained through 10-15 days p.i. Activation of monocytes with bacterial lipopolysaccharide, which resulted in activation of nuclear transcription factor kappaB (NF-kappaB) plus elevation of nitric oxide and type I interferon levels, reduced or eliminated WNV replication. These results suggest that immune cells of the peripheral blood may serve as target cells for initial replication of WNV and may play a role in subsequent viral dissemination. Furthermore, primary equine immune cell cultures represent a potentially useful model of a natural WNV host when testing compounds such as antivirals for use in WNV treatment.
Assuntos
Cavalos/virologia , Leucócitos Mononucleares/virologia , Replicação Viral , Vírus do Nilo Ocidental/fisiologia , Animais , Antígenos CD/metabolismo , Adesão Celular , Interferon Tipo I/metabolismo , Leucócitos Mononucleares/metabolismo , Lipopolissacarídeos , NF-kappa B/metabolismo , Testes de Neutralização , Óxido Nítrico/metabolismoRESUMO
Latent infection of sensory neurons and reactivation are necessary for maintenance of herpes simplex virus type 1 (HSV-1) in its host population. It has been proposed that the HSV-1 early gene, thymidine kinase (TK), may play an important regulatory role in this process. The authors used reporter transgenic mice to test whether sensory ganglia neurons could activate the HSV-1 TK reporter transgene in the absence of viral proteins. The reporter transgene was activated in subsets of neurons in the brain but was not activated in sensory ganglia neurons following a variety of experimental manipulations. These results do not support a role for TK in regulation of the latent viral genome.
Assuntos
Encéfalo/citologia , Herpes Simples/virologia , Herpesvirus Humano 1/genética , Neurônios Aferentes/fisiologia , Timidina Quinase/genética , Gânglio Trigeminal/citologia , Animais , Encéfalo/virologia , Genes Reporter , Camundongos , Camundongos Transgênicos , Neurônios Aferentes/virologia , Regiões Promotoras Genéticas , Transgenes/genética , Gânglio Trigeminal/virologia , Latência ViralRESUMO
The development of experimental Lyme arthritis has been correlated with the expression of a number of chemokines and cytokines, however, none of these have been measured directly from the arthritic joint. We examined the temporal expression of IL-1beta, IL-4, IL-6, IL-10, IL-12p70, GM-CSF, IFN-gamma, TNF-alpha, macrophage inflammatory protein-2, KC, macrophage inflammatory protein-1alpha, and monocyte chemoattractant protein-1 directly from the tibiotarsal joint in arthritis-resistant C57BL/6 (B6) and -susceptible C3H/He (C3H) mice. Only the chemokines KC and monocyte chemoattractant protein-1 were differentially expressed in joints of B6 and C3H mice and correlated with the development of Lyme arthritis. Infection of CXCR2(-/-) mice on either genetic background resulted in a significant decrease in the development of pathology, although infection of CCR2(-/-) mice had little or no effect. Neutrophils in CXCR2(-/-) mice were marginalized within blood vessels and could not enter the joint tissue. These results suggest that chemokine-mediated recruitment of neutrophils into the infected joint is a key requirement for the development of experimental Lyme arthritis.
Assuntos
Artrite Experimental/imunologia , Borrelia burgdorferi/imunologia , Quimiocina CCL2/biossíntese , Citocinas/biossíntese , Doença de Lyme/imunologia , Infiltração de Neutrófilos/imunologia , Receptores de Interleucina-8B/fisiologia , Membrana Sinovial/imunologia , Animais , Artrite Experimental/genética , Artrite Experimental/microbiologia , Artrite Experimental/patologia , Quimiocina CCL2/metabolismo , Quimiocina CXCL1 , Quimiocinas/biossíntese , Quimiocinas CXC , Citocinas/metabolismo , Citocinas/fisiologia , Feminino , Predisposição Genética para Doença , Membro Posterior , Doença de Lyme/genética , Doença de Lyme/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Camundongos Knockout , Infiltração de Neutrófilos/genética , Receptores CCR2 , Receptores de Quimiocinas/deficiência , Receptores de Quimiocinas/genética , Receptores de Interleucina-8B/deficiência , Receptores de Interleucina-8B/genética , Índice de Gravidade de Doença , Membrana Sinovial/metabolismo , Membrana Sinovial/patologiaRESUMO
Herpes simplex virus type 1 (HSV-1) immediate-early (IE) proteins are required for the expression of viral early and late proteins. It has been hypothesized that host neuronal proteins regulate expression of HSV-1 IE genes that in turn control viral latency and reactivation. We investigated the ability of neuronal proteins in vivo to activate HSV-1 IE gene promoters (ICP0 and ICP27) and a late gene promoter (gC). Transgenic mice containing IE (ICP0 and ICP27) and late (gC) gene promoters of HSV-1 fused to the Escherichia coli beta-galactosidase coding sequence were generated. Expression of the ICP0 and ICP27 reporter transgenes was present in anatomically distinct subsets of neurons in the absence of viral proteins. The anatomic locations of beta-galactosidase-positive neurons in the brains of ICP0 and ICP27 reporter transgenic mice were similar and included cerebral cortex, lateral septal nucleus, cingulum, hippocampus, thalamus, amygdala, and vestibular nucleus. Trigeminal ganglion neurons were positive for beta-galactosidase in adult ICP0 and ICP27 reporter transgenic mice. The ICP0 reporter transgene was differentially regulated in trigeminal ganglion neurons depending upon age. beta-galactosidase-labeled cells in trigeminal ganglia and cerebral cortex of ICP0 and ICP27 reporter transgenic mice were confirmed as neurons by double labeling with antineurofilament antibody. Nearly all nonneuronal cells in ICP0 and ICP27 reporter transgenic mice and all neuronal and nonneuronal cells in gC reporter transgenic mice were negative for beta-galactosidase labeling in the absence of HSV-1. We conclude that factors in neurons are able to differentially regulate the HSV-1 IE gene promoters (ICP0 and ICP27) in transgenic mice in the absence of viral proteins. These findings are important for understanding the regulation of the latent and reactivated stages of HSV-1 infection in neurons.
Assuntos
Regulação Viral da Expressão Gênica , Herpesvirus Humano 1/genética , Proteínas Imediatamente Precoces/metabolismo , Neurônios/fisiologia , Regiões Promotoras Genéticas , Animais , Encéfalo/citologia , Encéfalo/metabolismo , Genes Reporter , Herpes Simples/virologia , Herpesvirus Humano 1/metabolismo , Proteínas Imediatamente Precoces/genética , Camundongos , Camundongos Transgênicos , Transgenes , Gânglio Trigeminal/citologia , Gânglio Trigeminal/metabolismo , Ubiquitina-Proteína Ligases , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/metabolismo , beta-Galactosidase/genética , beta-Galactosidase/metabolismoRESUMO
Recently, we demonstrated that blocking the entry of neutrophils into Borrelia burgdorferi-infected joints in mice deficient in the chemokine receptor CXCR2 prevented the development of experimental Lyme arthritis. Neutrophils were marginalized in blood vessels at the site of infection but could not enter the joint tissue. In the present study, we treated both genetically arthritis-resistant DBA/2J (DBA) and arthritis-susceptible C3H/HeJ (C3H) mice with the neutrophil-depleting monoclonal antibody RB6-8C5 (RB6) to determine the effect on arthritis development. Surprisingly, both DBA and C3H mice treated with RB6 developed arthritis at 1 week postinfection, approximately 1 week earlier than the control-treated C3H mice. The early development of arthritis in the RB6-treated mice was accompanied by an influx into the joints of cells with ring-shaped polymorphonuclear leukocyte (PMN) cell morphology that were negative for the Gr-1 neutrophil maturation marker. RB6 treatment of mice also resulted in increased numbers of B. burgdorferi cells in the joints at 7 days postinfection and earlier expression of the chemokines KC and monocyte chemoattractant protein 1 in the joints compared to control-treated animals. Together, these results suggest that recruitment of neutrophils or PMN-like cells into an infected joint is a key requirement for Lyme arthritis development and that altered recruitment of these cells into the joints of arthritis-resistant mice can exacerbate the development of pathology.