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Host Response (host + response)
Selected AbstractsW2 Inflammation, Host Response, and VaccinesHELICOBACTER, Issue 5 2008Article first published online: 13 AUG 200 No abstract is available for this article. [source] Inflammation and Host ResponseHELICOBACTER, Issue 4 2006Article first published online: 13 JUL 200 First page of article [source] An In Vivo Study of the Host Response to Starch-Based Polymers and Composites Subcutaneously Implanted in RatsMACROMOLECULAR BIOSCIENCE, Issue 8 2005Alexandra P. Marques Abstract Summary: Implant failure is one of the major concerns in the biomaterials field. Several factors have been related to the fail but in general these biomaterials do not exhibit comparable physical, chemical or biological properties to natural tissues and ultimately, these devices can lead to chronic inflammation and foreign-body reactions. Starch-based biodegradable materials and composites have shown promising properties for a wide range of biomedical applications as well as a reduced capacity to elicit a strong reaction from immune system cells in vitro. In this work, blends of corn starch with ethylene vinyl alcohol (SEVA-C), cellulose acetate (SCA) and polycaprolactone (SPCL), as well as hydroxyapatite (HA) reinforced starch-based composites, were investigated in vivo. The aim of the work was to assess the host response evoked for starch-based biomaterials, identifying the presence of key cell types. The tissues surrounding the implant were harvested together with the material and processed histologically for evaluation using immunohistochemistry. At implant retrieval there was no cellular exudate around the implants and no macroscopic signs of an inflammatory reaction in any of the animals. The histological analysis of the sectioned interface tissue after immunohistochemical staining using ED1, ED2, CD54, MHC class II and ,/, antibodies showed positively stained cells for all antibodies, except for ,/, for all the implantation periods, where it was different for the various polymers and for the period of implantation. SPCL and SCA composites were the materials that stimulated the greatest cellular tissue responses, but generally biodegradable starch-based materials did not induce a severe reaction for the studied implantation times, which contrasts with other types of degradable polymeric biomaterials. [source] P04 Inflammation, Host response, Immunity, Animal Models, and VaccinesHELICOBACTER, Issue 4 2009Article first published online: 23 JUL 200 First page of article [source] Host response to the chondracanthid copepod Chondracanthus goldsmidi, a gill parasite of the striped trumpeter, Latris lineata (Forster), in TasmaniaJOURNAL OF FISH DISEASES, Issue 3 2010M Andrews Abstract The chondracanthid copepod, Chondracanthus goldsmidi is an ectoparasite of gills, inner opercula and nasal cavities of cultured striped trumpeter, Latris lineata (Forster). Whilst often present in high numbers (up to 60 parasites per host), little is known about its effect on striped trumpeter. In this study C. goldsmidi was associated with extensive epithelial hyperplasia and necrosis. Pathological changes were most pronounced near the parasite's attachment site, with papilloma-like growths surrounding the entire parasite resulting in deformation of the filament. The number of mucous cells increased near the parasite attachment sites on both the opercula and gills. Mast cells were absent in healthy gills; in contrast numerous mast cells were identified in the papilloma-like growths. Immunostaining identified piscidin-positive mast cells in the papilloma-like growths, presenting the first evidence of piscidin in the family Latridae. [source] Hepatic coccidiosis of the blue whiting, Micromesistius poutassou (Risso), and horse mackerel, Trachurus trachurus (L.), from Galician watersJOURNAL OF FISH DISEASES, Issue 6 2001E Abollo The aetiology, epidemiology and pathology of coccidiosis in commercially-exploited populations of Micromesistius poutassou and Trachurus trachurus from Galician waters were investigated. Sporogonic stages of Goussia clupearum and G. cruciata were found in the liver. Although the descriptive statistics of Goussia infrapopulations and demographic infection values were always higher in M. poutassou than in T. trachurus, parasite distribution was highly skewed for both coccidian species. In both fish species, the number of oöcysts showed a similar cumulative effect as parasite counts increased with increasing length and weight of fish, but did not change with host sex or sexual maturity. Pathological changes in infected liver parenchyma of both species were moderate (in T. trachurus) to severe (in M. poutassou), with greatly reduced livers in the most heavily infected fish. Large areas of liver tissue were replaced with oöcysts. Host response to infection included the formation of a fibrous capsule prior to infiltration by melanin and lymphocytes. Although post-recruit individuals of both fish species apparently tolerate a severe infection, there was statistical evidence of a serious contribution by the parasite to poor body condition in M. poutassou shown by changes in the hepatosomatic and K-Fulton indices and in the length- to-weight relationship. [source] Nurse Dose as a ConceptJOURNAL OF NURSING SCHOLARSHIP, Issue 1 2006Dorothy Brooten Purpose: To describe the concept of Nurse Dose. Methods: The concept of nurse dose has been identified from decades of clinical research as a concept essential in the delivery of safe and high quality health care. The components of nurse dose were conceptualized through review of the literature from nursing, medicine, and health services research. Findings: Nurse dose is conceptualized as having three equally essential components: dose, nurse, and host and host response. Dose in the macro view includes the number of nurses per patient or per population in cities, states, regions, or countries. Dose in a micro view includes the amount of nurse time and the number of contacts. The nurse component consists of the education, expertise, and experience of the nurse. Host is represented by an organization and its characteristics (culture, autonomy, practice control) in a macro view and by the patient and characteristics (beliefs, values, culture) in a micro view. Host response includes response to the autonomy and acceptability of the nurse. Conclusions: Greater nurse dose has been associated with decreases in patient mortality, morbidity, and healthcare costs. [source] Fungal endophytes in a 400-million-yr-old land plant: infection pathways, spatial distribution, and host responsesNEW PHYTOLOGIST, Issue 3 2007Michael Krings Summary ,,The Early Devonian Rhynie chert has been critical in documenting early land plant,fungal interactions. However, complex associations involving several fungi that enter into qualitatively different relationships with a single host plant and even interact with one another have not yet been detailed. ,,Here, we studied petrographic thin sections of the Rhynie chert plant Nothia aphylla. ,,Three fungal endophytes (co)occur in prostrate axes of this plant: narrow hyphae producing clusters of small spores; large spherical spores/zoosporangia; and wide aseptate hyphae that form intercellular vesicles in the cortex. Host responses on attack include bulging of infected rhizoids, formation of encasement layers around intracellular hyphae, and separation of infected from uninfected tissues by secondarily thickened cell walls. ,,A complex simultaneous interaction of N. aphylla with three endophytic fungi was discovered. The host responses indicate that some of the mechanisms causing host responses in extant plants were in place 400 million yr ago. Anatomical and life history features of N. aphylla suggest that this plant may have been particularly susceptible to colonization by fungi. [source] Host responses to a versatile commensal: PAMPs and PRRs interplay leading to tolerance or infection by Candida albicansCELLULAR MICROBIOLOGY, Issue 7 2009Thierry Jouault Summary The molecular interactions between commensal microorganisms and their host are basically different from those triggered by pathogens since they involve tolerance. When the commensal is genetically equipped to become an opportunistic pathogen, as is the case with Candida albicans, the picture becomes more complex. In this case, the balance between protection and invasion depends on host reactivity to altered microbial expression of ligands interacting with innate immune sensors. Based on experimental evidence obtained with C. albicans, we discuss the different molecular processes involved in the sensing of this important opportunistic human pathogen by a panel of pattern recognition receptors (PRRs) according to the numerous pathogen-associated molecular patterns (PAMPs) that can be exposed at its surface. Beneficial or deleterious immune responses that either maintain a commensal state or favour damage by the yeast result from this dynamic interplay. [source] Cutaneous melanoma: estimating survival and recurrence risk based on histopathologic featuresDERMATOLOGIC THERAPY, Issue 5 2005David E. Elder ABSTRACT:, The prognosis of melanoma is best understood in terms of a model of tumor progression, in which most melanomas may evolve through two major phases of progression: from a lesion that is nontumorigenic and has little or no capacity for metastasis; to a more advanced lesion that is tumorigenic and may have capacity for metastasis. The likelihood of metastasis varies with a number of attributes of the primary melanoma, including the phase of progression, the Breslow tumor thickness, mitotic rate, and host response to the tumorigenic compartment of the lesion, Clark's level of invasion, and other factors. When distant metastasis has occurred, the prognosis for the patient is very poor. In this monograph, the focus will be the discussion of factors related to the prognosis of melanomas that at diagnosis are clinically localized to the primary site. [source] The Drosophila PRR GNBP3 assembles effector complexes involved in antifungal defenses independently of its Toll -pathway activation functionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2010Alexey A. Matskevich Abstract The Drosophila Toll -signaling pathway controls the systemic antifungal host response. Gram-negative binding protein 3 (GNBP3), a member of the ,-glucan recognition protein family senses fungal infections and activates this pathway. A second detection system perceives the activity of proteolytic fungal virulence factors and redundantly activates Toll. GNBP3hades mutant flies succumb more rapidly to Candida albicans and to entomopathogenic fungal infections than WT flies, despite normal triggering of the Toll pathway via the virulence detection system. These observations suggest that GNBP3 triggers antifungal defenses that are not dependent on activation of the Toll pathway. Here, we show that GNBP3 agglutinates fungal cells. Furthermore, it can activate melanization in a Toll -independent manner. Melanization is likely to be an essential defense against some fungal infections given that the entomopathogenic fungus Beauveria bassiana inhibits the activity of the main melanization enzymes, the phenol oxidases. Finally, we show that GNBP3 assembles "attack complexes", which comprise phenoloxidase and the necrotic serpin. We propose that Drosophila GNBP3 targets fungi immediately at the inception of the infection by bringing effector molecules in direct contact with the invading microorganisms. [source] CTL quality and the control of human retroviral infectionsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2009Charles R. M. Bangham Abstract The CTL response plays a central part in deciding the outcome of viral infections. Evidence from host and viral genetics, gene expression microarrays and assays of T-cell phenotype and function indicate that individual differences in the efficiency of the virus-specific CTL response strongly determine the outcome of infection with the human retroviruses HTLV-1 and HIV-1. It is now believed that differences in anti-viral CTL efficiency or "quality" at the single-cell level are critical in determining the efficacy of the host response to viruses. However, it is difficult to identify and quantify the reasons for this apparent individual variation in CTL efficiency, because of the chronic course of infection and the dynamical complexity of the equilibrium that is established between the virus and the host immune response. Specifically, it is unclear whether the observed variations among infected hosts, i.e. in the frequency, phenotype and function or quality of T cells, are the causes or effects , or both , of the variation in the efficiency of virus control. [source] IL-22 and inflammation: Leukin' through a glass onionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2008Lauren A. Zenewicz Abstract IL-22 is a Th17,T-cell-associated cytokine that is highly expressed during chronic inflammation. IL-22 receptor expression is absent on immune cells, but is instead restricted to the tissues, providing signaling directionality from the immune system to the tissues. Through Stat3 signaling, IL-22 induces a variety of proliferative, anti-apoptotic, and anti-microbial pathways. IL-22 is bi-functional with both pro-inflammatory and protective effects on tissues depending on the inflammatory context. The cytokine plays a role both in the host response against extracellular pathogens and in the inflammation associated with autoimmune diseases. Therapeutics targeting IL-22 therefore may have promise for treating various chronic inflammatory diseases. [source] Mapping immune response profiles: The emerging scenario from helminth immunologyEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2007Alvaro Díaz Abstract Metazoan parasites of mammals (helminths) belong to highly divergent animal groups and yet induce a stereotypical host response: Th2-type immunity. It has long been debated whether this response benefits the host or the parasite. We review the current literature and suggest that Th2 immunity is an evolutionarily appropriate response to metazoan invaders both in terms of controlling parasites and repairing the damage they inflict. However, successful parasites induce regulatory responses, which become superimposed with, and control, Th2 responses. Beyond helminth infection, this superimposition of response profiles may be the norm: both Th1 and Th2 responses coexist with regulatory responses or, on the contrary, with the inflammatory Th17 responses. Thus, typical responses to helminth infections may differ from Th2-dominated allergic reactions in featuring not only a stronger regulatory component but also a weaker Th17 component. The similarity of immune response profiles to phylogenetically distinct helminths probably arises from mammalian evolution having hard-wired diverse worm molecules, plus tissue-damage signals, to the beneficial Th2 response, and from the convergent evolution of different helminths to elicit regulatory responses. We speculate that initiation of both Th2 and regulatory responses involves combinatorial signaling, whereby TLR-mediated signals are modulated by signals from other innate receptors, including lectins. [source] Interferon-, synergistically enhances induction of interleukin-6 by double stranded RNA in HeLa cellsFEBS JOURNAL, Issue 9 2000Jennifer L. Harcourt Double stranded RNA (dsRNA), an intermediate that is common during viral infection, directly induces much higher levels of expression of interleukin-6 (IL-6) mRNA than does the cytokine IL-1,. Interferon , (IFN,) by itself does not induce expression of IL-6; nonetheless, IFN, pretreatment dramatically enhances IL-6 induction by dsRNA but not by IL-1,. Mutation of either the activating transcription factor/cyclic AMP response element binding protein (ATF/CREB) or the NF-IL-6 binding element within the IL-6 promoter eliminates most responsiveness of CAT reporter constructs to either dsRNA or to IL-1,. IFN, pretreatment partially restores responsiveness to dsRNA but not to IL-1, when either the ATF/CREB site or the NF-IL-6 site is mutated, but at least one of these sites must be intact for responsiveness to be restored. Mutation of the ,B binding site in the IL-6 promoter eliminates responsiveness to either IL-1, or to dsRNA, and pretreatment with IFN, does not restore any responsiveness. Incubation with dsRNA leads to a decrease in protein translation, especially in cells that have been pretreated with IFN,. Nonetheless, IFN, pretreatment followed by dsRNA leads to very high IL-6 protein levels. These studies demonstrate that major differences exist in the induction of IL-6 at both the mRNA and protein levels by dsRNA compared to cytokines and that IFN, pretreatment selectively enhances IL-6 induction by dsRNA but not by IL-1,. The high levels of IL-6 expression that result when cells encounter class I IFN prior to dsRNA suggest a mechanism for a heightened host response to viral infection with heightened production of this pleotropic cytokine. [source] Neutrophil influx during non-typhoidal salmonellosis: who is in the driver's seat?FEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 3 2006Çagla Tükel Abstract A massive neutrophil influx in the intestine is the histopathological hallmark of Salmonella enterica serovar Typhimurium-induced enterocolitis in humans. Two major hypotheses on the mechanism leading to neutrophil infiltration in the intestinal mucosa have emerged. One hypothesis suggests that S. enterica serovar Typhimurium takes an active role in triggering this host response by injecting proteins, termed effectors, into the host cell cytosol which induce a proinflammatory gene expression profile in the intestinal epithelium. The second hypothesis suggests a more passive role for the pathogen by proposing that bacterial invasion stimulates the innate pathways of inflammation because the pathogen-associated molecular patterns of S. enterica serovar Typhimurium are recognized by pathogen recognition receptors on cells in the lamina propria. A review of the current literature reveals that, while pathogen recognition receptors are clearly involved in eliciting neutrophil influx during S. enterica serovar Typhimurium infection, a direct contribution of effectors in triggering proinflammatory host cell responses cannot currently be ruled out. [source] Pathogenesis and host response in Helicobacter infectionsFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 2 2005Karen A. Krogfelt No abstract is available for this article. [source] Pathogenesis and host response in Helicobacter infectionsFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 2 2001Leif Percival Andersen No abstract is available for this article. [source] Regulation of whole bacterial pathogen transcription within infected hostsFEMS MICROBIOLOGY REVIEWS, Issue 3 2008My-Van La Abstract DNA microarrays are a powerful and promising approach to gain a detailed understanding of the bacterial response and the molecular cross-talk that can occur as a consequence of host,pathogen interactions. However, published studies mainly describe the host response to infection. Analysis of bacterial gene regulation in the course of infection has confronted many challenges. This review summarizes the different strategies used over the last few years to investigate, at the genomic scale, and using microarrays, the alterations in the bacterial transcriptome in response to interactions with host cells. Thirty-seven studies involving 19 different bacterial pathogens were compiled and analyzed. Our in silico comparison of the transcription profiles of bacteria grown in broth or in contact with eukaryotic cells revealed some features commonly observed when bacteria interact with host cells, including stringent response and cell surface remodeling. [source] Helicobacter Hypothesis for Idiopathic Parkinsonism: Before and BeyondHELICOBACTER, Issue 5 2008R. John Dobbs Abstract We challenge the concept of idiopathic parkinsonism (IP) as inevitably progressive neurodegeneration, proposing a natural history of sequential microbial insults with predisposing host response. Proof-of-principle that infection can contribute to IP was provided by case studies and a placebo-controlled efficacy study of Helicobacter eradication. "Malignant" IP appears converted to "benign", but marked deterioration accompanies failure. Similar benefit on brady/hypokinesia from eradicating "low-density" infection favors autoimmunity. Although a minority of UK probands are urea breath test positive for Helicobacter, the predicted probability of having the parkinsonian label depends on the serum H. pylori antibody profile, with clinically relevant gradients between this "discriminant index" and disease burden and progression. In IP, H. pylori antibodies discriminate for persistently abnormal bowel function, and specific abnormal duodenal enterocyte mitochondrial morphology is described in relation to H. pylori infection. Slow intestinal transit manifests as constipation from the prodrome. Diarrhea may flag secondary small-intestinal bacterial overgrowth. This, coupled with genetically determined intense inflammatory response, might explain evolution from brady/hypokinetic to rigidity-predominant parkinsonism. [source] Deficiency in OGG1 Protects against Inflammation and Mutagenic Effects Associated with H. pylori Infection in MouseHELICOBACTER, Issue 5 2006Eliette Touati Abstract Background:,Helicobacter pylori infection is associated with gastric cancer. Study with the Big Blue mouse model has reported a mutagenic effect associated with the H. pylori infection, as a result in part of oxidative DNA damage. The present work investigates the consequences of a deficiency in the OGG1 DNA glycosylase, responsible for the excision of 8-oxo guanine, on the inflammatory and genotoxic host response to the infection. Materials and Methods:, Big Blue Ogg1,/, C57BL/6 mice were orally inoculated with H. pylori strain SS1 or vehicle only, and sacrificed after 1, 3, or 6 months. The serologic response, histologic lesions, mutant frequency, and spectra of mutations were assessed in the stomach and compared to what observed in the wild-type (Wt) context. Results:, Inflammatory lesions induced in the gastric mucosa of H. pylori -infected mice, corresponding to a moderate gastritis, were less severe in Ogg1,/, than in Wt Big Blue mice. Analysis of antimicrobial humoral immunity exhibited a lower IgG2a serum level (Th1 response) after 6 months of infection in Ogg1,/, than in the Wt mice. In these conditions, the H. pylori -SS1 infection in the Ogg1,/, mice did not induce a mutagenic effect at the gastric epithelial cells level, either after 3 or 6 months. Conclusions:, The inactivation of the OGG1 DNA glycosylase in mouse leads to less severe inflammatory lesions and abolished the mutagenic effect at the gastric epithelial cells level, induced by the H. pylori infection. These data suggest for the OGG1deficiency a protective role against inflammation and genotoxicity associated to the H. pylori infection. [source] Inflammation and host responseHELICOBACTER, Issue 5 2004Article first published online: 9 SEP 200 First page of article [source] Primary hepatocyte culture supports hepatitis C virus replication: A model for infection-associated hepatocarcinogenesis,HEPATOLOGY, Issue 6 2010Krishna Banaudha Analysis of progressive changes in hepatic gene expression that underlie hepatocarcinogenesis following hepatitis C virus (HCV) infection require examination of long-term cultures of normally differentiating primary human hepatocytes. We report a culture system of primary hepatocytes that support productive replication of infectious HCV. Hepatic functions were analyzed by reverse-transcription polymerase chain reaction amplification of total cell RNA from cultures maintained in serum-free defined medium for up to 190 days. Sustained hepatic function was assessed by expression of albumin, alpha-fetoprotein, cytochrome P4502E1, cytokeratin-18, type-1 collagen, transforming growth factor-beta 1, matrix metalloproteinase-2 (MMP-2), MMP-13, and interferon alpha-receptors 1 and 2. Normally differentiated human primary hepatocytes supported productive replication of infectious clones of HCV genotypes 1a, 1b, and 2a; virus infection was inhibited by antibodies against CD81 virus entry factor. Virus released into the culture media of HCV-infected primary hepatocytes repeatedly passage to naïve hepatocytes. Replication of the three HCV genotypes shows interferon sensitivity observed in natural infections. Conclusion: Sustained cultures of physiologic host cells for the propagation of infectious HCV strains should accelerate studies of host response to HCV infection and progressive liver disease. Hepatology 2010;51:1922,1932 [source] Signaling defects in anti-tumor T cellsIMMUNOLOGICAL REVIEWS, Issue 1 2008Alan B. Frey Summary: The immune response to cancer has been long recognized, including both innate and adaptive responses, showing that the immune system can recognize protein products of genetic and epigenetic changes in transformed cells. The accumulation of antigen-specific T cells within the tumor, the draining lymph node, and the circulation, either in newly diagnosed patients or resultant from experimental immunotherapy, proves that tumors produce antigens and that priming occurs. Unfortunately, just as obviously, tumors grow, implying that anti-tumor immune responses are either not sufficiently vigorous to eliminate the cancer or that anti-tumor immunity is suppressed. Both possibilities are supported by current data. In experimental animal models of cancer and also in patients, systemic immunity is usually not dramatically suppressed, because tumor-bearing animals and patients develop T-cell-dependent immune responses to microbes and to either model antigens or experimental cancer vaccines. However, inhibition of specific anti-tumor immunity is common, and several possible explanations of tolerance to tumor antigens or tumor-induced immunesuppression have been proposed. Inhibition of effective anti-tumor immunity results from the tumor or the host response to tumor growth, inhibiting the activation, differentiation, or function of anti-tumor immune cells. As a consequence, anti-tumor T cells cannot respond productively to developmental, targeting, or activation cues. While able to enhance the number and phenotype of anti-tumor T cells, the modest success of immunotherapy has shown the necessity to attempt to reverse tolerance in anti-tumor T cells, and the vanguard of experimental therapy now focuses on vaccination in combination with blockade of immunosuppressive mechanisms. This review discusses several potential mechanisms by which anti-tumor T cells may be inhibited in function. [source] Interleukin-10 in viral diseases and cancer: exiting the labyrinth?IMMUNOLOGICAL REVIEWS, Issue 1 2004Alain P. Vicari Summary:, Interleukin-10 (IL-10) is unique among cytokines, as it is considered both as a potent immunostimulatory and immunosuppressive factor. This complex biology has been particularly challenging when trying to define the useful or harmful role of IL-10 in chronic viral diseases and cancer. In the present review, we emphasize how these multiple roles define IL-10 as an adaptive molecule, constantly tuning the host response against dangerous and resourceful pathogens. [source] The role of B cells and alloantibody in the host response to human organ allograftsIMMUNOLOGICAL REVIEWS, Issue 1 2003Attapong Vongwiwatana Summary:, Some human organ transplants deteriorate slowly over a period of years, often developing characteristic syndromes: transplant glomerulopathy (TG) in kidneys, bronchiolitis obliterans in lungs, and coronary artery disease in hearts. In the past, we attributed late graft deterioration to ,chronic rejection', a distinct but mysterious immunologic process different from conventional rejection. However, it is likely that much of chronic rejection is explained by conventional T-cell-mediated rejection (TMR), antibody-mediated rejection (AMR), and other insults. Recently, criteria have emerged to now permit us to diagnose AMR in kidney transplants, particularly C4d deposition in peritubular capillaries and circulating antibody against donor human leukocyte antigens (HLA). Some cases with AMR develop TG, although the relationship of TG to AMR is complex. Thus, a specific diagnosis of AMR in kidney can now be made, based on graft damage, C4d deposition, and donor-specific alloantibodies. Criteria for AMR in other organs must be defined. Not all late rejections are AMR; some deteriorating organs probably have smoldering TMR. The diagnosis of late ongoing AMR raises the possibility of treatment to suppress the alloantibody, but efficacy of the available treatments requires further study. [source] Protective role of osteopontin in endodontic infectionIMMUNOLOGY, Issue 1 2010Susan R. Rittling Summary Endodontic infections are polymicrobial infections resulting in bone destruction and tooth loss. The host response to these infections is complex, including both innate and adaptive mechanisms. Osteopontin (OPN), a secreted, integrin-binding protein, functions in the regulation of immune responses and enhancement of leucocyte migration. We have assessed the role of OPN in the host response to endodontic infection using a well-characterized mouse model. Periapical bone loss associated with endodontic infection was significantly more severe in OPN-deficient mice compared with wild-type 3 weeks after infection, and was associated with increased areas of inflammation. Expression of cytokines associated with bone loss, interleukin-1, (IL-1,) and RANKL, was increased 3 days after infection. There was little effect of OPN deficiency on the adaptive immune response to these infections, as there was no effect of genotype on the ratio of bacteria-specific immunoglobulin G1 and G2a in the serum of infected mice. Furthermore, there was no difference in the expression of cytokines associated with T helper type 1/type2 balance: IL-12, IL-10 and interferon-,. In infected tissues, neutrophil infiltration into the lesion area was slightly increased in OPN-deficient animals 3 days after infection: this was confirmed by a significant increase in expression of neutrophil elastase in OPN-deficient samples at this time-point. We conclude that OPN has a protective effect on polymicrobial infection, at least partially because of alterations in phagocyte recruitment and/or persistence at the sites of infection, and that this molecule has a potential therapeutic role in polymicrobial infections. [source] Role of chemokine ligand 2 in the protective response to early murine pulmonary tuberculosisIMMUNOLOGY, Issue 4 2003Andre Kipnis Summary Chemokines play an important role in the development of immunity to tuberculosis. Chemokine ligand 2 (CCL2, JE, monocyte chemoattractant protein-1) is thought to be primarily responsible for recruiting monocytes, dendritic cells, natural killer cells and activated T cells, all of which play critical roles in the effective control of tuberculosis infection in mice. We show here that in mice in which the CCL2 gene was disrupted, low-dose aerosol infection with Mycobacterium tuberculosis resulted in fewer macrophages entering the lungs, but only a minor and transient increase in bacterial load in the lungs; these mice were still able to establish a state of chronic disease. Such animals showed similar numbers of activated T cells as wild-type mice, as determined by their expression of the CD44hi CD62lo phenotype, but a transient reduction in cells secreting interferon-,. These data indicate that the primary deficiency in mice unable to produce CCL2 is a transient failure to focus antigen-specific T lymphocytes into the infected lung, whereas other elements of the acquired host response are compensated for by different ligands interacting with the chemokine receptor CCR2. [source] RNA interference in ticks: a study using histamine binding protein dsRNA in the female tick Amblyomma americanumINSECT MOLECULAR BIOLOGY, Issue 3 2003M. N. Aljamali Abstract RNA interference (RNAi), a gene silencing process, has been recently exploited to determine gene function by degrading specific mRNAs in several eukaryotic organisms. We constructed a double stranded RNA (dsRNA) from a previously cloned putative Amblyomma americanum histamine binding protein (HBP) to test the significance of using this methodology in the assessment of the function and importance of gene products in ectoparasitic ticks. The female salivary glands incubated in vitro with HBP dsRNA had a significantly lower histamine binding ability. In addition, the injection of HBP dsRNA into the unfed females led both to a reduced histamine binding ability in the isolated salivary glands and to an aberrant tick feeding pattern or host response. Molecular data demonstrated less expression of the HBP mRNA in the RNAi group. Taken together, these results suggest that RNAi might be an important tool for assessing the significance of tick salivary gland secreted proteins modulating responses at the tick,host interface. [source] Efficacy of glucantime in the treatment of Old World cutaneous leishmaniasisINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 7 2009Rukhsana Firdous MPhil Background, Leishmaniasis is a parasitic disease caused by protozoa of the genus Leishmania. Depending on the parasite species and host response, the disease presents itself in different clinical forms. The cutaneous form of the disease is most common in the Old World. Pentavalent antimonials in the form of an injection represent the most widely used therapy for all clinical forms of the disease. As a result of reports on the development of resistance from various parts of the world, we thought it pertinent to determine its response in our region. Methods, Two hundred and seven military personnel with cutaneous leishmaniasis, caused by Leishmania major, were treated with glucantime according to the World Health Organization (WHO) recommended protocol. All patients were nonindigenous to the area and had moved from a nonendemic area to a highly endemic area. Results, Thirty-seven per cent of patients were cured within 15 days. The cure percentage reached 81% when 20 mg/kg/day was continued to 20 days. Twenty-five patients who failed to respond were subjected to a further course of glucantime injection. Sixteen responded by the 10th day of treatment, and the remaining nine were cured by completion of the second course, i.e. within 40 days. The drug was administered intramuscularly. The common side-effects noted were vertigo, headache, anorexia, temperature, and joint pain. Conclusion, Glucantime is still effective against Old World cutaneous leishmaniasis when used in the doses recommended by WHO. [source] | ||||||||||||||||||||||||||||||||||||||||