Abstract —Acute-phase proteins, which respond to systemic proinflammatory cytokines such as interleuken-6, are elevated in cardiovascular disease and predictive markers of future ischemic events, even over decades. This suggests a role for and/or acute phase proteins early lesion development. To explore this issue, we fed C57Bl/6 nonobese diabetic male mice high-fat (20% total fat, 1.5% cholesterol) diets ApoE-deficient both normal chow 6 21 weeks, injecting them weekly with either 5000 U...

Coxsackievirus infections have previously been shown to cause acute or chronic myocarditis in humans, and several mouse models established study the pathology of this disease. Myocardial injury may result from direct viral effects and/or be immune mediated. To determine relative roles these processes pathogenesis, we compared coxsackievirus B3 (CVB3) normal immuno-compromised transgenic knockout (ko) mice. CVB3 was able infect all strains used (C57BL/6, CD4ko, beta-microglobulin ko [beta...

Coxsackievirus B3 (CVB3) infections induce myocarditis in humans and mice. Little is known about the molecular characteristics of CVB3 that activate cellular immunity responsible for cardiac inflammation. Previous experiments have identified an antibody escape mutant (H310A1) a myocarditic variant (H3) attenuates potential virus mice spite ongoing viral replication heart. We cloned full-length infectious cDNA copies genome both wild-type H3 H310A1. Progeny viruses maintained attenuated...

Male and female BALB/c mice differ dramatically in susceptibility to myocarditis subsequent coxsackievirus B3 (CVB3) infection. CVB3 infection of male results substantial inflammatory cell infiltration the myocardium, virus-immune lymphocytes from these animals give predominantly a Th1 phenotypic response, as determined by predominant immunoglobulin G2a isotypic antibody production elevated numbers gamma interferon interleukin-2 (IL-2)-producing CD4+ T lymphocytes. Females infected with same...

Background —T cells are implicated in atherosclerosis, but little is known about the genetic control or molecular pathways, especially under conditions of mild hypercholesterolemia. Methods and Results —BALB/c mice, making a CD4+ Th2 (IL-4+) cell response, express both MHC class II antigens (IA d , IE ) atherosclerosis-resistant. C57Bl/6 mice produce Th1 (interferon [IFN]γ+) IA b no IE, atherosclerosis-prone. To evaluate T helper–cell phenotype fatty streak formation, wild-type +IE−)...

Oxidative stress oligomerizes an outer mitochondrial membrane protein to trigger antiviral response in the absence of infection.

Understanding the DNA elements that constitute and control regulatory genome is critical for appropriate therapeutic management of complex diseases. Here, using chromosome Y (ChrY) consomic mouse strains on C57BL/6J (B6) background, we show susceptibility to two diverse animal models autoimmune disease, experimental allergic encephalomyelitis (EAE) myocarditis, correlates with natural variation in copy number Sly Rbmy multicopy ChrY genes. On B6 possesses gene properties impact genome-wide...

Abstract Coxsackievirus B3 infections of C57BL/6 mice, which express the MHC class II IA but not IE Ag, results in virus replication heart minimal myocarditis. In contrast, Bl.Tg.Eα are mice transgenically induced to develop significant myocarditis upon infection. Despite this difference inflammatory damage, cardiac titers similar between and mice. Removing γδ T cells from either strain by genetic manipulation (γδ knockout(ko)) changes disease phenotype. ko show increased decreased...

Allergic airway inflammation and hyperreactivity are modulated by gammadelta T cells, but different experimental parameters can influence the effects observed. For example, in sensitized C57BL/6 BALB/c mice, transient depletion of all TCR-delta(+) cells just before challenge resulted hyperresponsiveness (AHR), caused hyporesponsiveness when initiated i.p. sensitization. Vgamma4(+) strongly suppressed AHR; their relieved suppression challenge, not sensitization, they AHR transferred into...

The Lyme disease spirochete Borrelia burgdorferi is the only known human pathogen that directly activates invariant NKT (iNKT) cells. number and activation kinetics of iNKT cells vary greatly among different strains mice. We now report role cell response in pathogenesis using C57BL/6 mice, a strain with optimal resistant to development spirochetal-induced inflammation. During experimental infection B6 mice B. burgdorferi, localize inflamed heart where they are activated by CD1d-expressing...

Both coxsackievirus B3 (CVB3) and influenza A virus (IAV; H1N1) produce sexually dimorphic infections in C57BL/6 mice. Gonadal steroids can modulate sex differences response to both viruses. Here, the effect of chromosomal complement viral infection was evaluated using four core genotypes (FCG) mice, where Sry gene is deleted from Y chromosome, some mice inserted into an autosomal chromosome. This results genotypes: XX or XY gonadal females (XXF XYF), males (XXM XYM). The FCG model permits...

Background Adaptive immunity has been implicated in atherosclerosis animal models and small clinical studies. Whether chronic immune activation is associated with otherwise healthy individuals remains underexplored. We hypothesized that of adaptive responses, as reflected by higher proportions circulating CD4+ memory cells lower naive cells, would be subclinical atherosclerosis. Methods Findings examined cross-sectional relationships T biomarkers inflammation, serologies, 912 participants...

T cells expressing the Vgamma4 T-cell receptor (TCR) promote myocarditis in coxsackievirus B3 (CVB3)-infected BALB/c mice. CD1, a major histocompatibility complex (MHC) class I-like molecule, is required for activation of Vgamma4(+) cells. Once activated, initiate through gamma interferon (IFN-gamma)-mediated induction CD4(+) helper type 1 (Th1) infected animal. These Th1 are an autoimmune CD8(+) alphabeta TCR(+) effector, which predominant pathogenic agent this model CVB3-induced...

Two variants of coxsackievirus B3 (CVB3) which differ dramatically in the ability to induce myocarditis BALB/c mice were studied. H3 virus infection murine monocytes vitro resulted release concentrations interleukin 1 (IL-1) and alpha/beta interferon that high compared with those cells infected H310A1 variant. In vivo, caused substantial inflammatory cell infiltration myocardium, lymphocytes from these animals gave predominantly Th1-cell responses either whole or overlapping peptides CVB3...

Immunologic similarities have been demonstrated between Coxsackievirus B3 (CVB3), group A streptococcal M protein, and cardiac myosin. Previous studies also shown that T lymphocytes obtained from CVB3-infected mice expressing the H-2k MHC haplotype gave an immunodominant proliferative response to NT4 peptide (GLKTENEGLKTENEGLKTE) of M5 protein. We now show can induce inflammatory heart disease in MRL/++ (H-2k) induction anergy this protects against CVB3-induced myocarditis. infected with...

Innate immunity promotes both the generation of autoimmunity and immunoregulation adaptive immunity. Transgenic mice expressing tumor necrosis factor-α (TNF-α) gene under cardiac myosin promoter (TNF1.6 mice) develop dilated cardiomyopathy. show extensive inflammation, suggesting that immunopathogenic mechanisms may promote Two coxsackievirus B3 (CVB3) variants infect replicate in heart. H3 variant is highly myocarditic, but H310A1 activates CD4 + T regulatory cells, which protect against...