YopP-expressing variant of Y. pestis activates a potent innate immune response affording cross-protection against yersiniosis and tularemia [corrected].

Plague, initiated by Yersinia pestis infection, is a rapidly progressing disease with a high mortality rate if not quickly treated. The existence of antibiotic-resistant Y. pestis strains emphasizes the need for the development of novel countermeasures against plague.

Frequency Analyses Can Be Improved by a Modified t-test in Sample-based Preclinical Efficacy Studies.

Unlabelled: Sample-based preclinical drug efficacy studies compare frequency (proportion) or incidences of successes within respective samples of test and control groups. The word success in principle refers to a protected (e.g.

A Lecinoxoid, an oxidized phospholipid small molecule, constrains CNS autoimmune disease.

Oxidized phospholipids (Ox-PLs) are generated in abundance at sites of inflammation. Recent studies have indicated that Ox-PLs may also exhibit anti-inflammatory activities. In this study, we investigated the beneficial effect of VB-201, a pure synthetic Ox-PL analog that we synthesized, on the development of a central nervous system (CNS) autoimmune inflammatory disease, in vivo.

The search for early markers of plague: evidence for accumulation of soluble Yersinia pestis LcrV in bubonic and pneumonic mouse models of disease.

Markers of the early stages of plague, a rapidly progressing deadly disease, are crucial for enabling the onset of an effective treatment. Here, we show that V-antigen protein (LcrV) is accumulated in the serum of Yersinia pestis-infected mice before bacterial colonization of the spleen and dissemination to blood, in a model of bubonic plague. LcrV accumulation is detected earlier than that of F1 capsular antigen, an established marker of disease.

Yersinia pestis endowed with increased cytotoxicity is avirulent in a bubonic plague model and induces rapid protection against pneumonic plague.

An important virulence strategy evolved by bacterial pathogens to overcome host defenses is the modulation of host cell death. Previous observations have indicated that Yersinia pestis, the causative agent of plague disease, exhibits restricted capacity to induce cell death in macrophages due to ineffective translocation of the type III secretion effector YopJ, as opposed to the readily translocated YopP, the YopJ homologue of the enteropathogen Yersinia enterocolitica Oratio8. This led us to suggest that reduced cytotoxic potency may allow pathogen propagation within a shielded niche, leading to increased virulence.

Neutralization of Yersinia pestis-mediated macrophage cytotoxicity by anti-LcrV antibodies and its correlation with protective immunity in a mouse model of bubonic plague.

Plague is a life-threatening disease caused by Yersinia pestis, for which effective-licensed vaccines and reliable predictors of in vivo immunity are lacking. V antigen (LcrV) is a major Y. pestis virulence factor that mediates translocation of the cytotoxic Yersinia protein effectors (Yops).

Effects of oleic acid and macrophage recruitment on cholesterol efflux in cell culture and in vivo.

Background And Aim: Monounsaturated fatty acids in diets are beneficial for the plasma lipoprotein profile, but studies in cell culture point out that they may also be detrimental by inhibiting cholesterol efflux to apo AI.

Methods And Results: In the present study we used mouse peritoneal macrophages, loaded with cholesterol and upregulated by cyclic AMP or by LXR/RXR ligands and compared the effect of oleic acid on cholesterol efflux to 3 different acceptors. Inhibition of cholesterol efflux by oleic acid ranged from 10 to 25% with HDL or 2.

Lower macrophage recruitment and atherosclerosis resistance in FVB mice.

The aim of this study was to compare some aspects of cholesterol accretion and cholesterol efflux in cellular components of the aortic wall derived from mice resistant or susceptible to atherosclerosis, FVB or C57BL, respectively. Cholesterol efflux, from cholesterol loaded smooth muscle cells or elicited macrophages, to apo A-I or HDL was similar in the two strains under basal conditions, and after cAMP or LXR upregulation. Recruitment of peritoneal macrophages, 3 days after thioglycollate injection, was 65% lower in FVB than in C57BL mice, commensurate with a 40% reduction in MCP-1 in peritoneal lavage.

LXR activation and cholesterol efflux from a lipoprotein depot in vivo.

Activation of LXR in cultured cells results in enhancement of cholesterol efflux to apo Al. To study cholesterol efflux, in vivo cationized LDL was injected into the rectus femoris muscle of mice to create a lipoprotein depot. LXR ligand TO901317, 10 mg/kg, was given by gavage for 8 days, starting 4 days after injection of the lipoprotein.

In CCR2-/- mice monocyte recruitment and egress of LDL cholesterol in vivo is impaired.

Recruitment of macrophages plays an important role in initiation of atheroma, but their involvement in cholesterol clearance during regression is unknown. We developed a mouse model to quantitate cholesterol clearance from a depot of cationized LDL injected into a leg muscle, which evokes a sterile inflammatory reaction. In the CCR2(-/-) mice, cholesterol clearance was significantly slower than in C57BL controls because of decrease in cholesteryl ester (CE) hydrolysis, which is mandatory prior to cholesterol efflux.