Regulation of macrophage function by interferon-gamma. Somatic cell genetic approaches in murine macrophage cell lines to mechanisms of growth inhibition, the oxidative burst, and expression of the chronic granulomatous disease gene.

Goldberg, Michael F.; Belkowski, L S; Bloom, Barry R.

doi:10.1172/jci114473

Cited by 54 publications

(31 citation statements)

References 32 publications

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“…IFN-y is a potent immunoregulatory cytokine. Major effects include enhancement and induction of class I and II MHC gene expression (41), activation of macrophages (42,43), and induction of molecules involved in T cell homing (44). Cytokines such as IFN-y usually act locally, and their production in vivo is poorly reflected in body fluids such as serum or CSF.…”

Section: Discussionmentioning

confidence: 99%

Autoreactive T lymphocytes in multiple sclerosis determined by antigen-induced secretion of interferon-gamma.

Olsson¹,

Zhi²,

Höjeberg³

et al. 1990

J. Clin. Invest.

344

160

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Multiple sclerosis (MS) is a disease with unknown cause characterized by inflammation and demyelination in the central nervous system. Although an autoimmune pathogenesis has been suggested, there are no conclusive data on the number of T cells autoreactive with myelin antigens in MS compared to controls. We showed that T lymphocytes secreting interferony in response to possible target autoantigens are severalfold more common among PBL mononuclear cells in patients with MS than in patients with aseptic meningitis and tension headache. On average T cells reactive with myelin basic protein (MBP), two different MBP peptides, or with proteolipid protein amounted to 2.7-5.2/105 PBL from MS patients. MBPreactive T cells were still more frequent among mononuclear cells isolated from the cerebrospinal fluid (CSF; 185/10O CSF cells). We concluded that T cells reactive with myelin autoantigens are strongly increased in MS. This approach to detect them could allow definition of immunodominant T cell epitopes in individual MS patients, and thereby enable further development towards specific immunotherapy. (J. Clin. Invest. 1990. 86:981-985.)

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Section: Discussionmentioning

confidence: 99%

Autoreactive T lymphocytes in multiple sclerosis determined by antigen-induced secretion of interferon-gamma.

Olsson¹,

Zhi²,

Höjeberg³

et al. 1990

J. Clin. Invest.

344

160

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“…on May 11, 2018 by guest http://iai.asm.org/ (14,22). Trypan blue exclusion was used to evaluate viability of J774A.16 and J774D.9 cells in the presence of deferoxamine.…”

Section: Vol 76 2008 Role Of Iron-regulated Genes In C Burnetii Pamentioning

confidence: 99%

Limited Role for Iron Regulation in Coxiella burnetii Pathogenesis

Briggs

Pul

Seshadri³

et al. 2008

Infect Immun

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In gram-negative bacteria, iron acquisition proteins are commonly regulated by Fur (ferric uptake regulator), which binds iron-regulated promoters (the Fur box). We hypothesized that Coxiella burnetii requires iron and employs an iron-regulatory system and used various approaches to define a Fur regulon. Cloned C. burnetii fur complemented an Escherichia coli fur deletion mutant. A ferrous iron transporter gene (CBU1766), a putative iron binding protein-encoding gene (CBU0970), and a cation efflux pump gene (CBU1362) were identified by genome annotation and using a Fur titration assay. Bioinformatically predicted Fur box-containing promoters were tested for transcriptional control by iron. Five genes demonstrated at least a twofold induction with minimal iron. Putatively regulated genes were evaluated in a two-plasmid regulator/promoter heterologous expression system. These data suggested a very limited Fur-regulated system in C. burnetii. In an in vitro tissue culture model, a significant increase in bacterial growth was observed with infected cells treated with deferoxamine in comparison to growth under iron-replete conditions. In an iron-overloaded animal model in vivo, the level of bacterial growth detected in the iron-injected animals was significantly decreased in comparison to growth in control animals. In a low-iron-diet animal model, a significant increase in splenomegaly was observed, but no significant change in bacterial growth was identified. The small number of predicted iron acquisition systems, few Fur-regulated genes, and enhanced replication under a decreased iron level predict a requirement of a low level of iron for survival, perhaps to avoid creation of additional reactive oxygen radicals.

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“…ROS are strongly induced in macrophages by IFN-␥ (15,27). As serovar Typhimurium has a preference to infect macrophages in vivo (14,33), this could lead to damage of the viral DNA before the virus would initiate its replication.…”

Section: Virus Reconstitution In Vivo By Serovar Typhimurium Carryingmentioning

confidence: 99%

Vaccination of Mice with Bacteria Carrying a Cloned Herpesvirus Genome Reconstituted In Vivo

Čičin-Šain¹,

Brune

Bubić

et al. 2003

J Virol

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Bacterial delivery systems are gaining increasing interest as potential vaccination vectors to deliver either proteins or nucleic acids for gene expression in the recipient. Bacterial delivery systems for gene expression in vivo usually contain small multicopy plasmids. We have shown before that bacteria containing a herpesvirus bacterial artificial chromosome (BAC) can reconstitute the virus replication cycle after cocultivation with fibroblasts in vitro. In this study we addressed the question of whether bacteria containing a single plasmid with a complete viral genome can also reconstitute the viral replication process in vivo. We used a natural mouse pathogen, the murine cytomegalovirus (MCMV), whose genome has previously been cloned as a BAC in Escherichia coli. In this study, we tested a new application for BAC-cloned herpesvirus genomes. We show that the MCMV BAC can be stably maintained in certain strains of Salmonella enterica serovar Typhimurium as well and that both serovar Typhimurium and E. coli harboring the single-copy MCMV BAC can reconstitute a virus infection upon injection into mice. By this procedure, a productive virus infection is regenerated only in immunocompromised mice. Virus reconstitution in vivo causes elevated titers of specific anti-MCMV antibodies, protection against lethal MCMV challenge, and strong expression of additional genes introduced into the viral genome. Thus, the reconstitution of infectious virus from live attenuated bacteria presents a novel concept for multivalent virus vaccines launched from bacterial vectors.Live, attenuated bacteria have a potential to serve as vaccine vectors for the oral delivery of foreign proteins (29) or DNA (11,13,23). Oral vaccination procedures do not require educated personnel, and lyophilized bacterial preparations can be kept and distributed at room temperature, without the costly and difficult necessity of keeping the preparations cold. Moreover, oral vaccination can be performed simultaneously on large numbers of subjects, which should make it an efficient strategy for livestock vaccination.Live antiviral vaccines are generally considered more efficient than subunit or inactivated vaccines because they are more likely to induce a broad range of immune responses to the expressed gene products and provide a better protection. Furthermore, since these vaccines replicate in the recipient, the immunity they confer should be long lasting (39). Therefore, a bacterial vaccination vector delivering an attenuated, yet infectious virus may present the basis for efficient vaccines that are easy to store, distribute, and administer.Herpesviruses are important pathogens for humans and livestock. We have previously shown that the large genomes of herpesviruses (up to 230 kb) can be cloned as bacterial artificial chromosomes (BACs) into Escherichia coli (1, 2, 24). Others have demonstrated that BAC DNA encoding the genome of a herpesvirus can induce specific protective immunity (35,36). However, in these experiments, the BAC DNA was isolated from bac...

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Regulation of macrophage function by interferon-gamma. Somatic cell genetic approaches in murine macrophage cell lines to mechanisms of growth inhibition, the oxidative burst, and expression of the chronic granulomatous disease gene.

Cited by 54 publications

References 32 publications

Autoreactive T lymphocytes in multiple sclerosis determined by antigen-induced secretion of interferon-gamma.

Autoreactive T lymphocytes in multiple sclerosis determined by antigen-induced secretion of interferon-gamma.

Limited Role for Iron Regulation in Coxiella burnetii Pathogenesis

Vaccination of Mice with Bacteria Carrying a Cloned Herpesvirus Genome Reconstituted In Vivo

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