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Ana-Carolina Oliveira Bruna C. de Alencar Fanny Tzelepis Weberton Klezewsky Raquel N. da Silva Fabieni S. Neves Gisele S. Cavalcanti Silvia Boscardin Marise P. Nunes Marcelo F. Santiago Alberto Nóbrega Maurício M. Rodrigues Maria Bellio 《PLoS pathogens》2010,6(4)
The murine model of T. cruzi infection has provided compelling evidence that development of host resistance against intracellular protozoans critically depends on the activation of members of the Toll-like receptor (TLR) family via the MyD88 adaptor molecule. However, the possibility that TLR/MyD88 signaling pathways also control the induction of immunoprotective CD8+ T cell-mediated effector functions has not been investigated to date. We addressed this question by measuring the frequencies of IFN-γ secreting CD8+ T cells specific for H-2Kb-restricted immunodominant peptides as well as the in vivo Ag-specific cytotoxic response in infected animals that are deficient either in TLR2, TLR4, TLR9 or MyD88 signaling pathways. Strikingly, we found that T. cruzi-infected Tlr2−/−, Tlr4−/−, Tlr9−/
− or Myd88−/− mice generated both specific cytotoxic responses and IFN-γ secreting CD8+ T cells at levels comparable to WT mice, although the frequency of IFN-γ+CD4+ cells was diminished in infected Myd88−/− mice. We also analyzed the efficiency of TLR4-driven immune responses against T. cruzi using TLR4-deficient mice on the C57BL genetic background (B6 and B10). Our studies demonstrated that TLR4 signaling is required for optimal production of IFN-γ, TNF-α and nitric oxide (NO) in the spleen of infected animals and, as a consequence, Tlr4−/− mice display higher parasitemia levels. Collectively, our results indicate that TLR4, as well as previously shown for TLR2, TLR9 and MyD88, contributes to the innate immune response and, consequently, resistance in the acute phase of infection, although each of these pathways is not individually essential for the generation of class I-restricted responses against T. cruzi. 相似文献
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Verbal cues modulate hedonic perception of odors in 5-year-old children as well as in adults 总被引:1,自引:0,他引:1
The judgment of pleasantness/unpleasantness is the prominent reaction to the olfactory world. In human adults, the hedonic valence of odor perception is affected by various factors, among which is an individual's lexical knowledge about smells. The present study examined whether such top-down effects of lexical knowledge on hedonic judgment of olfactory input are similar in children (5-6 years) and adults (20-25 years). In both groups, the lexical knowledge was found to influence the perception of the least emotional (or most neutral) odors: the pleasantness of the smells of banana and mint was enhanced when participants were given the corresponding odor label before olfactory sensation. These results lend support to the notion that, during childhood, smells are not only encoded perceptually but that verbal encoding also steers contextual effects that may be prominent factors in the early memorization and categorization of odors. 相似文献
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Co-localization of CENP-C and CENP-H to discontinuous domains of CENP-A chromatin at human neocentromeres 总被引:4,自引:0,他引:4
Alonso A Fritz B Hasson D Abrusan G Cheung F Yoda K Radlwimmer B Ladurner AG Warburton PE 《Genome biology》2007,8(7):R148
Background
Mammalian centromere formation is dependent on chromatin that contains centromere protein (CENP)-A, which is the centromere-specific histone H3 variant. Human neocentromeres have acquired CENP-A chromatin epigenetically in ectopic chromosomal locations on low-copy complex DNA. Neocentromeres permit detailed investigation of centromeric chromatin organization that is not possible in the highly repetitive alpha satellite DNA present at endogenous centromeres. 相似文献58.
Fanny Chaffanel Florence Charron-Bourgoin Virginie Libante Nathalie Leblond-Bourget Sophie Payot 《Applied and environmental microbiology》2015,81(12):4155-4163
The diversity of clinical (n = 92) and oral and digestive commensal (n = 120) isolates of Streptococcus salivarius was analyzed by multilocus sequence typing (MLST). No clustering of clinical or commensal strains can be observed in the phylogenetic tree. Selected strains (92 clinical and 46 commensal strains) were then examined for their susceptibilities to tetracyclines, macrolides, lincosamides, aminoglycosides, and phenicol antibiotics. The presence of resistance genes tet(M), tet(O), erm(A), erm(B), mef(A/E), and catQ and associated genetic elements was investigated by PCR, as was the genetic linkage of resistance genes. High rates of erythromycin and tetracycline resistance were observed among the strains. Clinical strains displayed either the erm(B) (macrolide-lincosamide-streptogramin B [MLSB] phenotype) or mef(A/E) (M phenotype) resistance determinant, whereas almost all the commensal strains harbored the mef(A/E) resistance gene, carried by a macrolide efflux genetic assembly (MEGA) element. A genetic linkage between a macrolide resistance gene and genes of Tn916 was detected in 23 clinical strains and 5 commensal strains, with a predominance of Tn3872 elements (n = 13), followed by Tn6002 (n = 11) and Tn2009 (n = 4) elements. Four strains harboring a mef(A/E) gene were also resistant to chloramphenicol and carried a catQ gene. Sequencing of the genome of one of these strains revealed that these genes colocalized on an IQ-like element, as already described for other viridans group streptococci. ICESt3-related elements were also detected in half of the isolates. This work highlights the potential role of S. salivarius in the spread of antibiotic resistance genes both in the oral sphere and in the gut. 相似文献
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Identification of NADPH oxidase as a key mediator in the post‐ischemia‐induced sequestration and degradation of the GluA2 AMPA receptor subunit 下载免费PDF全文
Phillip H. Beske Nicole M. Byrnes Fanny Astruc‐Diaz Darrell A. Jackson 《Journal of neurochemistry》2015,132(5):504-519
A hallmark of ischemic/reperfusion injury is a change in subunit composition of synaptic 2‐amino‐3‐(3‐hydroxy‐5‐methylisoazol‐4‐yl)propionic acid receptors (AMPARs). This change in AMPAR subunit composition leads to an increase in surface expression of GluA2‐lacking Ca2+/Zn2+ permeable AMPARs. These GluA2‐lacking AMPARs play a key role in promoting delayed neuronal death following ischemic injury. At present, the mechanism(s) responsible for the ischemia/reperfusion‐induced subunit composition switch and degradation of the GluA2 subunit remain unclear. In this study, we investigated the role of NADPH oxidase, and its importance in mediating endocytosis and subsequent degradation of the GluA2 AMPAR subunit in adult rat hippocampal slices subjected to oxygen–glucose deprivation/reperfusion (OGD/R) injury. In hippocampal slices pre‐treated with the NADPH oxidase inhibitor apocynin attenuated OGD/R‐mediated sequestration of GluA2 and GluA1 as well as prevent the degradation of GluA2. We provide compelling evidence that NADPH oxidase mediated sequestration of GluA1‐ and GluA2‐ involved activation of p38 MAPK. Furthermore, we demonstrate that inhibition of NADPH oxidase blunts the OGD/R‐induced association of GluA2 with protein interacting with C kinase‐1. In summary, this study identifies a novel mechanism that may underlie the ischemia/reperfusion‐induced AMPAR subunit composition switch and a potential therapeutic target.