We previously described an escape mechanism exploited by Mycobacterium tuberculosis (Mtb) to prevent the generation of fully competent dendritic cells (DC). We have now tested the effect of isolated mycobacterial components on human monocyte differentiation into DC and demonstrated that cell wall (CW)-associated alpha-glucan induces monocytes to differentiate into DC (Glu-MoDC) with the same altered phenotype and functional behaviour of DC derived from Mtb-infected monocytes (Mt-MoDC). In fact, Glu-MoDC lack CD1 molecule expression, fail to upregulate CD80 and produce IL-10 but not IL-12. We also showed that Glu-MoDC are not able to prime effector T cells or present lipid antigens to CD1-restricted T-cell clones. Thus, we propose a mechanism of Mtb-monocyte interaction mediated by CW-associated alpha-glucan, which allows the bacterium to evade both innate and acquired immune responses. 相似文献
Transposable elements (TEs) represent more than 45% of the human and mouse genomes. Both parasitic and mutualistic features
have been shown to apply to the host-TE relationship but a comprehensive scenario of the forces driving TE fixation within
mammalian genes is still missing. 相似文献
The antibody-mediated targeted delivery of cytokines to sites of disease is a promising avenue for cancer therapy, but it
is largely unexplored for the treatment of chronic inflammatory conditions. Using both radioactive and fluorescent techniques,
the human monoclonal antibodies L19 and G11 (specific to two markers of angiogenesis that are virtually undetectable in normal
adult tissues) were found to selectively localize at arthritic sites in the murine collagen-induced model of rheumatoid arthritis
following intravenous (i.v.) administration. The same animal model was used to study the therapeutic action of the L19 antibody
fused to the cytokines IL-2, tumour necrosis factor (TNF) and IL-10. Whereas L19–IL-2 and L19–TNF treatment led to increased
arthritic scores and paw swellings, the fusion protein L19–IL-10 displayed a therapeutic activity, which was superior to the
activity of IL-10 fused to an antibody of irrelevant specificity in the mouse. The anti-inflammatory cytokine IL-10 has been
investigated for the treatment of patients with rheumatoid arthritis, but clinical development plans have been discontinued
because of a lack of efficacy. Because the antigen recognised by L19 is strongly expressed at sites of arthritis in humans
and identical in both mice and humans, it suggests that the fusion protein L19–IL-10 might help overcome some of the clinical
limitations of IL-10 and provide a therapeutic benefit to patients with chronic inflammatory disorders, including arthritis. 相似文献
The redox enzyme phospholipid hydroperoxide glutathione peroxidase (PHGPx) has emerged as one of the most significant selenoenzymes in mammals, corroborated by early embryonic lethality of PHGPx null mice. PHGPx is one of five selenium-dependent glutathione peroxidases and the second glutathione peroxidase to be discovered in 1982. PHGPx has a particular position within this family owing to its peculiar structural and catalytic properties, its multifaceted roles during male gametogenesis, and its necessity for early mouse development. Interestingly, mice devoid of endogenous glutathione die at the same embryonic stage as PHGPx-deficient mice compatible with the hypothesis that a similar phenotype of embryonic lethality may be provoked by PHGPx deficiency and lack of its reducing substrate glutathione. Various gain- and loss-of-function approaches in mice have provided some insights into the physiological functions of PHGPx. These include a protective role for PHGPx in response to irradiation, increased resistance of transgenic PHGPx mice to toxin-induced liver damage, a putative role in various steps of embryogenesis, and a contribution to sperm chromatin condensation. The expression of three forms of PHGPx and early embryonic lethality call for more specific studies, such as tissue-specific disruption of PHGPx, to precisely understand the contribution of PHGPx to mammalian physiology and under pathological conditions. 相似文献
Here, we show that the murine neurodegenerative disease mdf (autosomal recessive mouse mutant 'muscle deficient') is caused by a loss-of-function mutation in Scyl1, disrupting the expression of N-terminal kinase-like protein, an evolutionarily conserved putative component of the nucleocytoplasmic transport machinery. Scyl1 is prominently expressed in neurons, and enriched at central nervous system synapses and neuromuscular junctions. We show that the pathology of mdf comprises cerebellar atrophy, Purkinje cell loss and optic nerve atrophy, and therefore defines a new animal model for neurodegenerative diseases with cerebellar involvement in humans. 相似文献
The diversity of deep-sea cultivable bacteria was studied in seven sediment samples of the Colombian Caribbean. Three hundred and fifty two marine bacteria were isolated according to its distinct morphological character on the solid media, then DNA sequences of the 16S rRNA were amplified to identify the isolated strains. The identified bacterial were arranged in three phylogenetic groups, Firmicutes, Proteobacteria, and Actinobacteria, with 34 different OTUs defined at ≥?97% of similarity and 70 OTUs at ≥?98.65%, being the 51% Firmicutes, 34% Proteobacteria and 15% Actinobacteria. Bacillus and Fictibacillus were the dominant genera in Firmicutes, Halomonas and Pseudomonas in Proteobacteria and Streptomyces and Micromonospora in Actinobacteria. In addition, the strains were tested for biosurfactants and lipolytic enzymes production, with 120 biosurfactant producing strains (mainly Firmicutes) and, 56 lipolytic enzymes producing strains (Proteobacteria). This report contributes to the understanding of the diversity of the marine deep-sea cultivable bacteria from the Colombian Caribbean, and their potential application as bioremediation agents.