Home About us Contact
|
Home About us Contact | ||
|
|
||
Invading Pathogens (invading + pathogen)
Selected AbstractsToll-like receptors, endogenous ligands, and systemic autoimmune diseaseIMMUNOLOGICAL REVIEWS, Issue 1 2005Ian R. Rifkin Summary:, The critical role of Toll-like receptors (TLRs) as mediators of pathogen recognition by the innate immune system is now firmly established. Such recognition results in the initiation of an inflammatory immune response and subsequent instruction of the adaptive immune system, both of which are designed to rid the host of the invading pathogen. More controversial is the potential role of TLRs in the recognition of endogenous ligands and what effect this might have on the consequent development of autoimmune or other chronic sterile inflammatory disorders. An increasing number of studies implicate TLRs as being involved in the immune response to self-molecules that have in some way been altered from their native state or accumulate in non-physiologic sites or amounts, although questions have been raised about possible contaminants in certain of these studies. In this review, we discuss the evidence for endogenous ligand,TLR interactions with particular emphasis on mammalian chromatin, systemic lupus erythematosus, and atherosclerosis. Overall, the data support the general concept of a role for TLRs in the recognition of endogenous ligands. However, the precise details of the interactions and the extent to which they may contribute to the pathogenesis of human disease remain to be clarified. [source] Innate recognition of intracellular pathogens: detection and activation of the first line of defenseAPMIS, Issue 5-6 2009SIMON B. RASMUSSEN The innate immune system constitutes the first line of defense against infections and is also important for initiating the development of an adaptive immune response. The innate immune system recognizes microbial infection through germline-encoded pattern recognition receptors, which are responsible for decoding the microbial fingerprint and activating an appropriate response against the invading pathogen. In this review, we present and discuss current knowledge on how the innate immune system recognizes intracellular pathogens, activates intracellular signaling, induces gene expression, and orchestrates the microbicidal response against pathogens with a habitat within host cells. [source] Role of haem oxygenase-1 in microbial host defenceCELLULAR MICROBIOLOGY, Issue 2 2009Su Wol Chung Summary Haem oxygenase (HO)-1 is a cytoprotective enzyme that plays a critical role in defending the body against oxidant-induced injury during inflammatory processes. HO catalydes the degradation of haem to carbon monoxide (CO), biliverdin and ferrous iron. Biliverdin is converted to bilirubin, a potent endogenous antioxidant. CO has a number of biological functions, including anti-inflammatory properties. In various models of disease, HO-1 is known to play a critical role by ameliorating the pathological consequences of injury. In many of these models, the beneficial effects of HO-1 and its products of haem catabolism are by suppressing an inflammatory response. However, when investigating diseases due to microbial infections, inhibition of the inflammatory response could disrupt the ability of the immune system to eradicate an invading pathogen. Thus, questions remain regarding the role of HO-1 in microbial host defence. This microreview will address our present understanding of HO-1 and its functional significance in a variety of microbial infections. [source] The CD8+ dendritic cell subsetIMMUNOLOGICAL REVIEWS, Issue 1 2010Ken Shortman Summary:, Mouse lymphoid tissues contain a subset of dendritic cells (DCs) expressing CD8, together with a pattern of other surface molecules that distinguishes them from other DCs. These molecules include particular Toll-like receptor and C-type lectin pattern recognition receptors. A similar DC subset, although lacking CD8 expression, exists in humans. The mouse CD8+ DCs are non-migrating resident DCs derived from a precursor, distinct from monocytes, that continuously seeds the lymphoid organs from bone marrow. They differ in several key functions from their CD8, DC neighbors. They efficiently cross-present exogenous cell-bound and soluble antigens on major histocompatibility complex class I. On activation, they are major producers of interleukin-12 and stimulate inflammatory responses. In steady state, they have immune regulatory properties and help maintain tolerance to self-tissues. During infection with intracellular pathogens, they become major presenters of pathogen antigens, promoting CD8+ T-cell responses to the invading pathogens. Targeting vaccine antigens to the CD8+ DCs has proved an effective way to induce cytotoxic T lymphocytes and antibody responses. [source] Dissecting innate immunity by germline mutagenesisIMMUNOLOGY, Issue 4 2008Sophie Rutschmann Summary The innate arm of our immune system is the first line of defence against infections. In addition, it is believed to drive adaptive immune responses, which help fight pathogens and provide long-term memory. As such, the innate immune system is instrumental for protection against pathogens that would otherwise destroy their host. Although our understanding of the innate immune components involved in pathogen sensing and fighting is improving, it is still limited. This is particularly exemplified by increased documentation of innate immune deficiencies in humans that often result in high and recurrent susceptibility to infections or even death, without the genetic cause being evident. To provide further insight into the mechanisms by which pathogen sensing and eradication occur, several strategies can be used. The current review focuses on the forward genetic approaches that have been used to dissect innate immunity in the fruit fly and the mouse. For both animal models, forward genetics has been instrumental in the deciphering of innate immunity and has greatly improved our understanding of how we respond to invading pathogens. [source] Transcriptional profiling of a mice plague model: insights into interaction between Yersinia pestis and its hostJOURNAL OF BASIC MICROBIOLOGY, Issue 1 2009Haihong Liu Abstract Despite the importance of pneumonic plague caused by Yersinia pestis, a few is known about the interaction between Y. pestis and its host at the molecular level during the pneumonic plague development. In this study, we employed an intranasally challenged plague model in mice for investigating the kinetics of the disease progression by transcriptional profiling of Y. pestis and mice using qRT-PCR and microarray, respectively. The increasing transcription of important virulence genes of Y. pestis and of mice genes involving in immune and inflammatory defensive responses, and responses to stimuli, presents an overview of interaction between Y. pestis and mice during development of pneumonic plague. The early and persisting up-regulation of caf 1, psa A and lcr V in vivo indicated their role in resisting the host innate immune responses. The up-regulation of fur, ybt A and hms H in vivo reflected the ability of Y. pestis for acquiring iron. The transcription regulators, including pho P, oxy R and omp R, were up-regulated during plague development, suggesting their roles in interaction between Y. pestis and mice. Many genes encoding cytokines, such as IL2, IL-1B, CXCL2, CXCL5, CCL20, CD14 and TNFRSF13B, were up-regulated during the infection, confirming the report that they are important mediators to activate host responses to invading pathogens. The up-regulation of some genes encoding important virulent factors of Y. pestis and expression alterations of some genes encoding cytokines in the host reflect the interaction between the pathogen and the host, which will help us better understand plague pathogenesis. (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Toll-like receptors and their role in gastrointestinal diseaseJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 6 2009Adam G Testro Abstract The innate immune response to invading pathogens is centred upon a family of non-clonal, germline-encoded pattern recognition receptors (PRRs), the Toll-like receptors (TLRs). These provide specificity for a vast range of microbial pathogens, and offer an immediate anti-microbial response system. Thirteen mammalian TLRs have been described; 10 are expressed in humans, each responsible for the recognition of distinct, invariant microbial structures originating from bacteria, viruses, fungi and protozoa. The two most thoroughly studied are TLR4 and TLR2, the PRRs for Gram-negative and Gram-positive bacterial products, respectively. TLR4 is also the major receptor recognising endogenous ligands released from damaged or dying cells. Activation of a TLR by its relevant ligand rapidly ignites a complex intracellular signaling cascade that ultimately results in upregulation of inflammatory genes and production of proinflammatory cytokines, interferons and recruitment of myeloid cells. It also stimulates expression, upon antigen presenting cells, of co-stimulatory molecules required to induce an adaptive immune response. Whilst a robust TLR response is critical for survival and defence against invading pathogens, inappropriate signaling in response to alterations in the local microflora environment can be detrimental. Such ,unhelpful TLR responses' could form the basis for a large number of gastrointestinal and liver disorders, including inflammatory bowel disease, viral hepatitis, autoimmune liver diseases and hepatic fibrosis. As our understanding of TLRs expands, the pathogenesis of a number of gastrointestinal disorders will be further elucidated, and this offers potential for specific therapies aimed directly at TLR signaling. [source] Critical roles for thrombin in acute and chronic inflammationJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2009D. CHEN Summary., Thrombin can amplify inflammation induced by other stimuli, either through ischemia (consequent upon thrombosis), indirectly through generation of downstream mediators such as activated protein C, or directly via signals through protease activated receptors (PAR). This paper will summarize recent data from our laboratory indicating that thrombin is required to initiate CCR2-dependent leukocyte recruitment and that it is the principal determinant of the outcome after vascular injury, via PAR-1 activation of a distinct subset of smooth muscle cell progenitors. In both, tissue factor (TF) initiates thrombin generation and the thrombin acts locally, exemplifying that the initiation phase can generate autocrine or paracrine signalling molecules. Thrombin is an important constituent of innate immunity, able to amplify and modify responses to invading pathogens or tissue damage. With novel anti-thrombin therapeutics and agents to target PAR, a new understanding of the importance of thrombin may allow the development of innovative anti-inflammatory strategies. [source] Cytotoxic T-cell-mediated defense against infections in human liver transplant recipientsLIVER TRANSPLANTATION, Issue 2 2007Koichi Tanaka Previous studies have shown that postoperative infection is highest in transplant recipients with preexisting high levels of cytotoxic T lymphocytes (CTLs). To study this phenomenon, 106 adult liver transplant recipients were divided into 3 groups, based on hierarchical clustering of the CD3+CD8+CD45 isoform fractions prior to living donor liver transplantation (LDLT). Group I had the highest naive T-cell levels (subset CD45RO,CCR7+), Group II had the highest effector/memory (EM) T-cell levels (subset CD45RO+CCR7,), and Group III had the highest effector T-cell levels (subset CD45RO,CCR7,). In Group I, CTLs upregulated in response to invading pathogens much earlier and more rapidly than the other groups; this response was associated with CD4+ T-cell help, downregulation of CD27+CD28+ subsets, and upregulation of interferon-gamma and perforin expression. In contrast, in Groups II and III, CTLs upregulated slowly following persistent viral infection and did not respond efficiently to acute infection. In addition, Group II's cytolytic responses were due mainly to upregulation of the CD8+ EM T-cell fraction, whereas Group III's cytolytic responses were attributable to upregulation of effector T cells. The prevalence of EM or effector T cells was dependent on differentiation of the CD8+ phenotype before LDLT. In conclusion, in most infected transplant recipients who died, generation of CD8+ CTLs had been suppressed without associated CD4+ T-cell help. Liver Transpl 13:287,293, 2007. © 2007 AASLD. [source] Collectin structure: A reviewPROTEIN SCIENCE, Issue 9 2000Kjell Håkansson Abstract Colleetins are animal calcium dependent lectins that target the carbohydrate structures on invading pathogens, resulting in the agglutination and enhanced clearance of the microorganism. These proteins form trimers that may assemble into larger oligomers. Each polypeptide chain consists of four regions: a relatively short N-terminal region, a collagen like region, an ,-helical coiled-coil, and the lectin domain. Only primary structure data are available for the N-terminal region, while the most important features of the collagen-like region can be derived from its homology with collagen. The structures of the ,-helical coiled-coil and the lectin domain are known from crystallographic studies of mannan binding protein (MBP) and lung surfactant protein D (SP-D). Carbohydrate binding has been structurally characterized in several complexes between MBP and carbohydrate; all indicate that the major interaction between carbohydrate and collectin is the binding of two adjacent carbohydrate hydroxyl group to a collectin calcium ion. In addition, these hydroxyl groups hydrogen bond to some of the calcium amino acid ligands. While each collectin trimer contains three such carbohydrate binding sites, deviation from the overall threefold symmetry has been demonstrated for SP-D, which may influence its binding properties. The protein surface between the three binding sites is positively charged in both MBP and SP-D. [source] REVIEW ARTICLE: Toll-Like Receptors, Inflammation and Tumor in the Human Female Reproductive TractAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2009Li Yu Abstract, Toll-like receptors are an important family of pattern recognition receptors. They recognize microbial conserved components and trigger protective responses to the invading pathogens, which constitute a major part of the innate immune system. Toll-like receptors are mainly expressed in immune cells. The current evidences demonstrate that Toll-like receptors are present in some epithelial cells and epithelium derived tumor cells. The expression of Toll-like receptors in these cells is related to infection and inflammation, and tumor progression as well. Genital mucosal epithelium is the first line in defense of microorganism invasion in the female reproductive tract. Toll-like receptors expressed in the genital tract have been implicated in many aspects of reproductive physiology and pathology in the female. In the current review, we will focus on the expression of Toll-like receptors in the female genital mucosa and its association with anti-infection immunity and tumorigenesis. [source] How to outwit the enemy: dendritic cells face Salmonella,APMIS, Issue 9 2006Review article Salmonella enterica serovar Typhi causes typhoid fever, a serious life-threatening systemic infection. In mice, a similar disease is caused by Salmonella enterica serovar Typhimurium. During typhoid fever, soon after attachment to the mucosal surface of the gut, bacteria come into contact with the dendritic cells (DCs). The ability to sample antigens, process and present them to na,Ðve and mature T cells, in the context of major histocompatibility complex molecules, makes DCs indispensable for mounting a specific and efficient immune response to invading pathogens. These bacteria, however, have evolved a number of mechanisms to interfere with or subvert DC functions. This review aims to describe how Salmonella clashes with dendritic cells at different stages of infection as well as the war strategies of these two opposing sides. [source] Crystallization of a nonclassical Kazal-type Carcinoscorpius rotundicauda serine protease inhibitor, CrSPI-1, complexed with subtilisinACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 5 2009Shenoy Rajesh Tulsidas Serine proteases play a major role in host,pathogen interactions. The innate immune system is known to respond to invading pathogens in a nonspecific manner. The serine protease cascade is an essential component of the innate immune system of the horseshoe crab. The serine protease inhibitor CrSPI isoform 1 (CrSPI-1), a unique nonclassical Kazal-type inhibitor of molecular weight 9.3,kDa, was identified from the hepatopancreas of the horseshoe crab Carcinoscorpius rotundicauda. It potently inhibits subtilisin and constitutes a powerful innate immune defence against invading microbes. Here, the cloning, expression, purification and cocrystallization of CrSPI-1 with subtilisin are reported. The crystals diffracted to 2.6,Å resolution and belonged to space group P21, with unit-cell parameters a = 73.8, b = 65.0, c = 111.9,Å, , = 95.4°. The Matthews coefficient (VM = 2.64,Å3,Da,1, corresponding to 53% solvent content) and analysis of the preliminary structure solution indicated the presence of one heterotrimer (1:2 ratio of CrSPI-1:subtilisin) and one free subtilisin molecule in the asymmetric unit. [source] Evasion of innate and adaptive immune responses by influenza A virusCELLULAR MICROBIOLOGY, Issue 7 2010Mirco Schmolke Summary Host organisms have developed sophisticated antiviral responses in order to defeat emerging influenza A viruses (IAVs). At the same time IAVs have evolved immune evasion strategies. The immune system of mammals provides several lines of defence to neutralize invading pathogens or limit their replication. Here, we summarize the mammalian innate and adaptive immune mechanisms involved in host defence against viral infection and review strategies by which IAVs avoid, circumvent or subvert these mechanisms. We highlight well-characterized, as well as recently described features of this intriguing virus-host molecular battle. [source] How important are Toll-like receptors for antimicrobial responses?CELLULAR MICROBIOLOGY, Issue 8 2007Susan Carpenter Summary The innate immune system is the primary line of defence against invading pathogenic microbes. Toll-like receptors (TLRs) are a family of membrane receptors which play a pivotal role in sensing a wide range of invading pathogens including bacteria, fungi and viruses. TLR-deficient mice have provided us with immense knowledge on the functioning of individual TLRs. Dysregulation of TLR signalling is linked with a number of disease conditions. Disease models have helped show that targeting components of TLR signalling cascades could lead to novel therapies in the treatment of infectious diseases. In this review we focus on the evidence provided to date to explain just how important TLRs are in host defence against microbial pathogens. [source] Characterization of mediators of microbial virulence and innate immunity using the Caenorhabditis elegans host,pathogen modelCELLULAR MICROBIOLOGY, Issue 7 2003Rosanna A. Alegado Summary The soil-borne nematode, Caenorhabditis elegans, is emerging as a versatile model in which to study host,pathogen interactions. The worm model has shown to be particularly effective in elucidating both microbial and animal genes involved in toxin-mediated killing. In addition, recent work on worm infection by a variety of bacterial pathogens has shown that a number of virulence regulatory genes mediate worm susceptibility. Many of these regulatory genes, including the PhoP/Q two-component regulators in Salmonella and LasR in Pseudomonas aeruginosa, have also been implicated in mammalian models suggesting that findings in the worm model will be relevant to other systems. In keeping with this concept, experiments aimed at identifying host innate immunity genes have also implicated pathways that have been suggested to play a role in plants and animals, such as the p38 MAP kinase pathway. Despite rapid forward progress using this model, much work remains to be done including the design of more sensitive methods to find effector molecules and further characterization of the exact interaction between invading pathogens and C. elegans' cellular components. [source] | ||||||||||||||||