Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0009450 (infectious diseases)
 83,438 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cell wall of the oomycete plant pathogen Phytophthora parasitica var. nicotianae contains a protein called CBEL that shows cellulose-binding (CB), elicitor (E) of defense in plants and lectin-like (L) activities. The biological role of this molecule in Phytophthora was investigated by generating transgenic strains suppressed in CBEL expression. Phenotypic characterization of these strains showed that they were severely impaired in adhesion to a cellophane membrane, differentiation of lobed structures in contact with cellophane, and formation of branched aggregating hyphae on cellophane and on flax cellulose fibres. Infection assays revealed that the strains suppressed in CBEL expression were not greatly affected in pathogenicity and formed branched aggregating hyphae in contact with the roots of the host plant, thereby indicating that CBEL is involved in the perception of cellulose rather than in the morphogenesis of hyphal aggregates. Interestingly, the absence of CBEL was correlated with abnormal formation of papillae-like cell wall thickenings in vitro, suggesting that CBEL is involved in cell wall deposition in Phytophthora. Reverse genetics in oomycetes has long been hampered by their diploid nature and difficulties in transformation and regeneration. The gene inactivation approach reported in this work provides the first direct evidence for intrinsic functions of an elicitor and cell wall protein in oomycetes.
 ...
PMID:The CBEL glycoprotein of Phytophthora parasitica var-nicotianae is involved in cell wall deposition and adhesion to cellulosic substrates. 1241 1

A number of recent studies have demonstrated the importance of prolactin as a key mediator in immune-neuroendocrine communication. Using a whole blood assay and various concentrations of prolactin, we stimulated cell cultures with either the plant lectin PHA or the endotoxin LPS, a widespread agent in common infectious diseases. Studying 15 healthy blood donors we found that human recombinant prolactin, at concentrations from 5 ng/ml to 100 ng/ml, significantly amplified IFN-gamma yields after stimulation with either PHA or LPS. PHA-stimulated cultures revealed a significant dose-dependent enhancement of IFN-gamma release. Our results indicate that prolactin can upregulate IFN-gamma secretion from immune cells in whole blood cell cultures in response to both PHA or LPS. Since IFN-gamma is suspected to play a key role in the cytokine cascade, amplifying the toxic effect of other pro-inflammatory cytokines and ultimately leading to augmented inflammatory tissue damage, our findings point to a modulatory role of prolactin in infection. Special interest should therefore be directed towards any naturally occurring hyperprolactinemia, caused for instance by stress, a number of drugs, and some chronic diseases.
 ...
PMID:Prolactin induces enhanced interferon gamma release in peripheral whole blood after stimulation with either PHA or LPS. 1243 72

Large clonal expansions of peripheral CD8+ T cells carrying receptors for single epitopes of CMV and EBV are common in the elderly and may be associated with an immune risk phenotype predicting mortality. Here we show that the frequency of CD8+ T cells expressing the inhibitory killer cell lectin-like receptor G1 (KLRG1), a marker of cells unable to undergo further clonal expansion, was markedly elevated in CD8+ T cells from old donors. Moreover, tetramer staining revealed that the elevated frequency of CMV-specific CD8+ T cells in the elderly was due to an accumulation of cells bearing this dominant negative receptor. The fraction of CMV-specific T cells able to secrete interferon-gamma after specific antigenic stimulation was significantly lower in the elderly than in the young, although the total number of functional cells was comparable. Therefore, the majority of the clonally expanded virus-specific CD8+ cells in the elderly was dysfunctional. Thus, T cell responses are altered in the aged by an accumulation of replicatively senescent dysfunctional T cells carrying receptors for persistent herpes viruses. The presence of clonal expansions of such virus-specific cells may shrink the available repertoire for other antigens and contribute to the increased incidence of infectious disease in the elderly.
 ...
PMID:Age-associated accumulation of CMV-specific CD8+ T cells expressing the inhibitory killer cell lectin-like receptor G1 (KLRG1). 1513 Jun 84

Mannose-binding lectin (MBL) is a pattern recognition molecule of the innate immune system. It belongs to the collectin family of proteins in which lectin (carbohydrate-recognition) domains are found in association with collagenous structures. In man, these proteins include serum MBL, lung surfactant protein A (SP-A) and lung surfactant protein D (SP-D). MBL binds to a range of sugars including N-acetyl-D-glucosamine, mannose, N-acetyl-mannosamine, fucose and glucose. This permits the protein to interact with a wide selection of viruses, bacteria, yeasts, fungi and protozoa decorated with such sugars. Unlike the other collectins, MBL bound to microbial surfaces is able to activate the complement system in an antibody and C1-independent manner. This activation is mediated by complexes of MBL with a serine protease called MBL-associated serine protease 2 (MASP-2), which specifically cleaves C4 and C2 to create a C3 convertase enzyme. MBL may also interact directly with cell surface receptors and thereby promote opsonophagocytosis by a complement-independent pathway. It has been suggested that MBL plays an important role in the first hours/days of any primary immune response to a sugar decorated pathogen. This provides the host with a first-line of defence before the adaptive immune system becomes operative and in humans may be particularly important between 6 and 18 months of age when the adaptive system is still immature. MBL deficiency is one of the most common human immunodeficiencies and arises primarily from three single point mutations in exon 1 of the MBL-2 gene. These mutations result in a failure to assemble fully functional multimeric protein. Several studies have shown that deficiency of MBL increases the overall susceptibility of an individual to infectious disease. The most striking example of this is the association of acute respiratory tract infections with MBL deficiency in early childhood. In contrast, there is evidence that for some intracellular parasites MBL deficiency may be protective and this might explain the high frequency of MBL mutations in sub-Saharan Africa and South America. Increasingly, there is evidence that the association between MBL levels and disease is complex. For example, the protein appears to influence the severity of several diseases. The mechanism whereby MBL exerts such effects is unclear but one possibility is through a dose-dependent modulation of pro-inflammatory cytokines.
 ...
PMID:The role of mannose-binding lectin in health and disease. 1456 88

C-type lectins such as DC-SIGN and L-SIGN, which bind mannose-enriched carbohydrate modifications of host and pathogen proteins, have been shown to bind glycoproteins of several viruses and facilitate either cis or trans infection. DC-SIGN and L-SIGN are expressed in several early targets of arbovirus infection, including dendritic cells (DCs) and cells of the reticuloendothelial system. In the present study, we show that DC-SIGN and L-SIGN can function as attachment receptors for Sindbis (SB) virus, an arbovirus of the Alphavirus genus. Human monocytic THP-1 cells stably transfected with DC-SIGN or L-SIGN were permissive for SB virus replication, while untransfected controls were essentially nonpermissive. The majority of control THP-1 cells were permissive when attachment and entry steps were eliminated through electroporation of virus transcripts. Infectivity for the DC-SIGN/L-SIGN-expressing cells was largely blocked by yeast mannan, EDTA, or a DC-SIGN/L-SIGN-specific monoclonal antibody. Infection of primary human DCs by SB virus was also dependent upon SIGN expression by similar criteria. Furthermore, production of virus particles in either C6/36 mosquito cells or CHO mammalian cells under conditions that limited complex carbohydrate content greatly increased SB virus binding to and infection of THP-1 cells expressing these lectins. C6/36-derived virus also was much more infectious for primary human DCs than CHO-derived virus. These results suggest that (i) lectin molecules such as DC-SIGN and L-SIGN may represent common attachment receptor molecules for arthropod-borne viruses, (ii) arbovirus particles produced in and delivered by arthropod vectors may preferentially target vertebrate host cells bearing these or similar lectin molecules, and (iii) a cell line has been identified that can productively replicate alphaviruses but is deficient in attachment receptors.
 ...
PMID:DC-SIGN and L-SIGN can act as attachment receptors for alphaviruses and distinguish between mosquito cell- and mammalian cell-derived viruses. 1458 39

When the adaptive immune response is either immature or compromised, the innate immune system constitutes the principle defense against infection. Mannose-binding lectin (MBL) is a C-type serum lectin that plays a central role in the innate immune response. MBL binds microbial surface carbohydrates and mediates opsonophagocytosis directly and by activation of the lectin complement pathway. A wide variety of clinical isolates of bacteria, fungi, viruses, and parasites are bound by MBL. Three polymorphisms in the structural gene MBL2) and 2 promoter gene polymorphisms are commonly found that result in production of low serum levels of MBL. Clinical studies have shown that MBL insufficiency is associated with bacterial infection in patients with neutropenia and meningococcal sepsis. Low MBL levels appear to predispose persons to HIV infection. Numerous other potential infectious disease associations have been described. Therapy to supplement low MBL levels is being explored using either plasma-derived or recombinant material.
 ...
PMID:Impact of mannose-binding lectin on susceptibility to infectious diseases. 1461 73

Lectins are phylogenetically ancient proteins that have specific recognition and binding functions for complex carbohydrates of glycoconjugates, i. e., of glycoproteins, proteoglycans/glycosaminoglycans and glycolipids. This class of proteins mediates important processes of adhesion and communication both inside and outside cells. A large variety of lectins are expressed in the human organism. This article reviews the current knowledge of human lectins with a focus on biochemistry and pathobiochemistry (principles of protein glycosylation and defects of glycosylation as a basis of disease) and cell biology (protein sorting, exocytosis and endocytosis, apoptosis, cell adhesion, cell differentiation, and malignant transformation). The clinical significance of lectin-glycoconjugate interactions is described by example of inflammatory diseases, defects of immune defense, autoimmunity, infectious diseases, and tumor invasion/metastasis. Moreover, therapeutic perspectives of novel drugs that interfere with lectin-carbohydrate interactions are discussed.
 ...
PMID:[Human lectins and their correspondent glycans in cell biology and clinical medicine]. 1468 73

The characteristics and primary structure of AJL-1, one of the lectins in the skin mucus of the Japanese eel (Anguilla japonica), were examined. This lectin exhibited beta-galactoside specific activity in a Ca2+ independent manner. We previously reported that its molecular mass was 16,091Da, although it was approximately 30 kDa as determined by gel filtration, indicating that it is a homodimer having non-covalent bonds. This lectin was composed of 142 amino acid residues having no half-cystinyl residues, and showed homology to members of the galectin family, especially to proto-type galectins. Gene expression of this lectin was detected in skin only, and relative expression was high in an individual that exhibited resistance to infectious disease. AJL-1 showed agglutinating activity against pathogenic bacteria, Streptococcus difficile. This suggests that AJL-1 functions as an important defensive factor at the body surface.
 ...
PMID:Characteristics and primary structure of a galectin in the skin mucus of the Japanese eel, Anguilla japonica. 1469 18

Targeting of specific pathogens to FcRs on immune effector cells by using bispecific Abs was reported to result in effective killing of the pathogens, both in vitro and in vivo. Instead of targeting a specific pathogen to an FcR, we assessed whether a broad spectrum of pathogens can be targeted to an FcR using surfactant protein D (SP-D). SP-D is a collectin that binds a great variety of pathogens via its carbohydrate recognition domain. A recombinant trimeric fragment of SP-D (rfSP-D), consisting of the carbohydrate recognition domain and neck domain of human SP-D, was chemically cross-linked to the Fab' of an Ab directed against the human Fc alpha RI (CD89). In vitro, the chimeric rfSP-D/anti-CD89 protein enhanced uptake of Escherichia coli, Candida albicans, and influenza A virus by human neutrophils. Blocking of the interaction between rfSP-D/anti-CD89 and either the pathogen or CD89 abolished its stimulatory effect on pathogen uptake by neutrophils. In addition, rfSP-D/anti-CD89 stimulated killing of E. coli and C. albicans by neutrophils and enhanced neutrophil activation by influenza A virus. In conclusion, rfSP-D/anti-CD89 effectively targeted three structurally unrelated pathogens to neutrophils. (Col)lectin-based chimeric proteins may thus offer promise for therapy of infectious disease.
 ...
PMID:Effective targeting of pathogens to neutrophils via chimeric surfactant protein D/anti-CD89 protein. 1506 73

Infection of mice with the nematode parasite Trichinella spiralis induces changes in the proteome of the jejunal epithelium, including substantial up-regulation of a novel variant of interlectin. In this study we sequence this novel lectin, termed intelectin-2, and compare expression levels during T. spiralis infection of resistant (BALB/c) with susceptible (C57BL/10) mouse strains. Intelectin-2 was cloned and sequenced from BALB/c mRNA extracted on day 14 of infection, and was found to have 91% amino acid identity with intelectin (within our study termed intelectin-1). Intelectin-2 transcripts were up-regulated early (day 3) during infection with T. spiralis in BALB/c mice, suggesting an innate response, and levels remained high through to day 14 (time of parasite rejection). Immunohistochemistry of jejunal sections with a rabbit polyclonal Ab to Xenopus laevis 35-kDa cortical granule lectin (XL35; 68% identity with intelectin-2) followed a similar pattern, with intense labeling of goblet and Paneth cells at day 14. However, intelectin-2 transcripts and protein were absent, and immunohistochemistry negative when C57BL/10 mice were infected with T. spiralis. Genomic PCR and Southern blotting confirmed that the intelectin-2 gene is absent from the C57BL/10 genome. The presence of intelectin-2 in resistant BALB/c mice, its absence from the susceptible C57BL/10 strain and the kinetics of its up-regulation during T. spiralis infection suggest that this novel lectin may serve a protective role in the innate immune response to parasite infection.
 ...
PMID:Innate BALB/c enteric epithelial responses to Trichinella spiralis: inducible expression of a novel goblet cell lectin, intelectin-2, and its natural deletion in C57BL/10 mice. 1526 22


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>