Search results for "Diphtheria Toxin"

Novel Microglia Depletion Systems: A Genetic Approach Utilizing Conditional Diphtheria Toxin Receptor Expression and a Pharmacological Model Based on…

2019

Microglia are the main population of macrophage residing in the central nervous system (CNS). Depletion experiments gave important insights into the physiology and function of microglia in healthy and diseased CNS. Ablation of microglia can be achieved by application of pharmacological or genetic tools. Here, we describe two approaches to ablate microglia: an efficient genetic model that utilizes DTRMG mouse line that has diphtheria toxin receptor (DTR) expression regulated by the promoter activity of the fractalkine receptor (CX3CR1) gene, and a pharmacological model that utilizes the blocking of macrophage colony-stimulating factor 1 receptor (CSF-1R) with a blocking antibody. Both the ad…

Gamma interferon blocks gammaherpesvirus reactivation from latency in a cell type-specific manner

2007

Gammaherpesviruses are important pathogens whose lifelong survival in the host depends critically on their capacity to establish and reactivate from latency, processes regulated by both viral genes and the host immune response. Previous work has demonstrated that gamma interferon (IFN-gamma) is a key regulator of chronic infection with murine gammaherpesvirus 68 (gammaHV68), a virus that establishes latent infection in B lymphocytes, macrophages, and dendritic cells. In mice deficient in IFN-gamma or the IFN-gamma receptor, gammaHV68 gene expression is altered during chronic infection, and peritoneal cells explanted from these mice reactivate more efficiently ex vivo than cells derived from…

Glycoconjugate vaccines and immune interactions, and implications for vaccination schedules.

2011

Conjugate vaccines using diphtheria toxoid variant (CRM(197)), diphtheria toxoid and tetanus toxoid (TT) as carrier protein may induce immune interactions (interference or impairment as measured by lower antibody levels, or enhancement [higher antibody levels]) when coadministered with other vaccines. Immune enhancement occurs when two TT conjugates are coadministered. CRM(197) conjugate vaccines induce immune bystander interference when given with diphtheria-tetanus-acellular pertussis vaccines, which reduces responses to coadministered Haemophilus influenzae type b vaccine conjugated to TT. These bystander effects are greater as the amount of CRM(197) administered increases. When large am…

2013

B cells were first discovered as antibody producing cells, as B-1 B cells and finally as effector cells. In recent years their capacity to serve as antigen presenting cells is increasingly appreciated, and better tools are needed to study their function. We have previously described a new mouse model, the iDTR mice, that allow for the Cre-mediated expression of the diphtheria toxin receptor, thus rendering cells that express the Cre-recombinase sensitivity to diphtheria toxin. Herein we describe a new mouse line, the B-DTR mice, where the CD19-Cre was crossed to the iDTR mice. B-DTR allows for the efficient and cost-effective depletion of different B cell subpopulations, but only partially …

Staphyloccal alpha toxin

1998

A Cre-inducible diphtheria toxin receptor mediates cell lineage ablation after toxin administration.

2004

A new system for lineage ablation is based on transgenic expression of a diphtheria toxin receptor (DTR) in mouse cells and application of diphtheria toxin (DT). To streamline this approach, we generated Cre-inducible DTR transgenic mice (iDTR) in which Cre-mediated excision of a STOP cassette renders cells sensitive to DT. We tested the iDTR strain by crossing to the T cell- and B cell-specific CD4-Cre and CD19-Cre strains, respectively, and observed efficient ablation of T and B cells after exposure to DT. In MOGi-Cre/iDTR double transgenic mice expressing Cre recombinase in oligodendrocytes, we observed myelin loss after intraperitoneal DT injections. Thus, DT crosses the blood-brain bar…

A Transgenic Mouse Model of Inducible Macrophage Depletion

2009

Whether the wound macrophage is a key regulatory inflammatory cell type in skin repair has been a matter of debate. A transgenic mouse model mediating inducible macrophage depletion during skin repair has not been used to date to address this question. Here, we specifically rendered the monocyte/macrophage leukocyte lineage sensitive to diphtheria toxin by expressing the lysozyme M promoter-driven, Cre-mediated excision of a transcriptional STOP cassette from the simian DT receptor gene in mice (lysM-Cre/DTR). Application of diphtheria toxin to lysM-Cre/DTR mice led to a rapid reduction in both skin tissue and wound macrophage numbers at sites of injury. Macrophage-depleted mice revealed a …

Genetic ablation of mast cells redefines the role of mast cells in skin wound healing and bleomycin-induced fibrosis.

2014

Conclusive evidence for the impact of mast cells (MCs) in skin repair is still lacking. Studies in mice examining the role of MC function in the physiology and pathology of skin regenerative processes have obtained contradictory results. To clarify the specific role of MCs in regenerative conditions, here we used a recently developed genetic mouse model that allows conditional MC ablation to examine MC-specific functions in skin. This mouse model is based on the cell type–specific expression of Cre recombinase in connective tissue–type MCs under control of the Mcpt5 promoter and the Cre-inducible diphtheria toxin receptor–mediated cell lineage ablation by diphtheria toxin. In response to ex…

Prevalence of diphtheria toxin antibodies in human sera from a cross-section of the Italian population.

1999

Abstract A polycentric study was carried out between 1993 and 1995 in order to evaluate diphtheria immunity on a representative sample of population from different areas of Italy. To determine diphtheria antitoxin, sera from 5187 apparently healthy subjects, divided according to sex and age groups, were titrated using an ELISA indirect method. A basic protective titre of diphtheria antitoxin (>0.01 IU ml −1 ) was found in 4080 (78.6%) subjects. No statistically significant differences between males and females were observed. Our findings show that the proportion of susceptibles increases with age and a high proportion of adults no longer has diphtheria antitoxin at protective levels since t…

Immunity to diphtheria in the 3–19 year age group in Italy

1991

In Italy, immunization with diphtheria toxoid has been compulsory for all newborns since 1939. The last two clinical cases of diphtheria were reported in 1987. During the period 1987-1989, immunity against diphtheria was assessed by neutralization test in a random sample of 1740 healthy subjects 3-19 years old, from five geographical areas of Italy. Of the total population, 76.5% showed antibody levels considered to be protective (greater than or equal to 0.1 IU ml-1), 17.2% had a relative degree of protection (0.01-0.09 IU ml-1), and 6.3% lacked immunity (less than 0.01 IU ml-1). The percentage of unprotected subjects increased from 6.1% in the age group of 3-5 years to 11.4% in the age gr…