26 research outputs found
CX3CR1 knockout aggravates Coxsackievirus B3-induced myocarditis
Studies on inflammatory disorders elucidated the pivotal role of the
CX3CL1/CX3CR1 axis with respect to the pathophysiology and diseases
progression. Coxsackievirus B3 (CVB3)-induced myocarditis is associated with
severe cardiac inflammation, which may progress to heart failure. We therefore
investigated the influence of CX3CR1 ablation in the model of acute
myocarditis, which was induced by inoculation with 5x105 plaque forming units
of CVB3 (Nancy strain) in either CX3CR1-/- or C57BL6/j (WT) mice. Seven days
after infection, myocardial inflammation, remodeling, and titin expression and
phosphorylation were examined by immunohistochemistry, real-time PCR and Pro-Q
diamond stain. Cardiac function was assessed by tip catheter. Compared to WT
CVB3 mice, CX3CR1-/- CVB3 mice exhibited enhanced left ventricular expression
of inflammatory cytokines and chemokines, which was associated with an
increase of immune cell infiltration/presence. This shift towards a pro-
inflammatory immune response further resulted in increased cardiac fibrosis
and cardiomyocyte apoptosis, which was reflected by an impaired cardiac
function in CX3CR1-/- CVB3 compared to WT CVB3 mice. These findings
demonstrate a cardioprotective role of CX3CR1 in CVB3-infected mice and
indicate the relevance of the CX3CL1/CX3CR1 system in CVB3-induced
myocarditis
Strategies for optimizing the mechanical strengths of raw earth-based mortars
International audienc
Vibration of thermally postbuckled FG-GRC laminated plates resting on elastic foundations
Herpes simplex encephalitis in adult patients with MASP-2 deficiency.
We report here two cases of Herpes simplex virus encephalitis (HSE) in adult patients with very rare, previously uncharacterized, non synonymous heterozygous G634R and R203W substitution in mannan-binding lectin serine protease 2 (MASP2), a gene encoding a key protease of the lectin pathway of the complement system. None of the 2 patients had variants in genes involved in the TLR3-interferon signaling pathway. Both MASP2 variants induced functional defects in vitro, including a reduced (R203W) or abolished (G634R) protein secretion, a lost capability to cleave MASP-2 precursor into its active form (G634R) and an in vivo reduced antiviral activity (G634R). In a murine model of HSE, animals deficient in mannose binding lectins (MBL, the main pattern recognition molecule associated with MASP-2) had a decreased survival rate and an increased brain burden of HSV-1 compared to WT C57BL/6J mice. Altogether, these data suggest that MASP-2 deficiency can increase susceptibility to adult HSE