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Results for “host:pathogen interactions”

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PubMed2006

Microsatellite polymorphism across the M. tuberculosis and M. bovis genomes: implications on genome evolution and plasticity.

BACKGROUND: Microsatellites are the tandem repeats of nucleotide motifs of size 1-6 bp observed in all known genomes. These repeats show length polymorphism characterized by either insertion or deletion (indels) of the repeat units, which in and around the coding regions affect transcription and translation of genes. RESULTS: Systematic comparison of all the equivalent microsatellites in the coding regions of the three mycobacterial genomes, viz. Mycobacterium tuberculosis H37Rv, Mycobacterium tuberculosis CDC1551 and Mycobacterium bovis, revealed for the first time the presence of several polymorphic microsatellites. The coding regions affected by frame-shifts owing to microsatellite indels have undergone changes indicative of gene fission/fusion, premature termination and length variation. Interestingly, the genes affected by frame-shift mutations code for membrane proteins, transporters, PPE, PE_PGRS, cell-wall synthesis proteins and hypothetical proteins. CONCLUSION: This study has revealed the role of microsatellite indel mutations in imparting novel functions and a certain degree of plasticity to the mycobacterial genomes. There seems to be some correlation between microsatellite polymorphism and the variations in virulence, host-pathogen interactions mediated by surface antigen variations, and adaptation of the pathogens. Several of the polymorphic microsatellites reported in this study can be tested for their polymorphic nature by screening clinical isolates and various mycobacterial strains, for establishing correlations between microsatellite polymorphism and the phenotypic variations among these pathogens.

Bacterial Proteins↗

PubMed2002

Bench-to-bedside review: Toll-like receptors and their role in septic shock.

The Toll-like receptors (TLRs) are essential transmembrane signaling receptors of the innate immune system that alert the host to the presence of a microbial invader. The recent discovery of the TLRs has rapidly expanded our knowledge of molecular events that initiate host-pathogen interactions. These functional attributes of the cellular receptors provide insights into the nature of pattern recognition receptors that activate the human antimicrobial defense systems. The fundamental significance of the TLRs in the generation of systemic inflammation and the pathogenesis of septic shock is reviewed. The potential clinical implications of therapeutic modulation of these recently characterized receptors of innate immunity are also discussed.

Animals↗

PubMed2026

Clinical and genomic features of mitis group streptococcal bacteremia in patients with febrile neutropenia.

BACKGROUND: Viridans group streptococci (VGS) can cause the life-threatening viridans streptococcal shock syndrome (VSSS) in patients with febrile neutropenia (FN). The Mitis group, a major subgroup of VGS, is frequently implicated in these severe infections, but its specific clinical and genomic characteristics remain incompletely characterized, particularly in patients with FN. This study aimed to systematically describe these features in this population. METHODS: In this single-center retrospective study, we compared the clinical data and whole-genome sequencing (WGS) results of Mitis group streptococcal isolates from patients with and without FN. Virulence-associated and antimicrobial resistance genes were initially screened using a reference-based approach, followed by assembly-based reanalysis and manual sequence validation. RESULTS: Compared with the non-FN cohort (n = 34), the FN cohort (n = 61) was significantly younger, had a higher prevalence of hematologic malignancy, and more frequently presented with primary bacteremia. VSSS occurred exclusively in the FN group (11.5%) and was associated with high mortality (14-day mortality, 42.9%), which did not correlate with in vitro antimicrobial susceptibility. Genomic analyses revealed marked diversity among isolates. Initial screening suggested variable detection of several virulence-associated loci, including pavA, slrA, and rfb-related loci; however, subsequent assembly-based analyses indicated that many apparent absences were attributable to extreme allelic divergence rather than true gene loss. No single virulence determinant clearly segregated with clinical severity. CONCLUSIONS: Mitis group bacteremia in patients with FN appears to be characterized by distinct clinical features and marked genomic diversity. Our findings suggest that the development of severe disease, including VSSS, may not be explained by microbial factors alone and potentially reflects complex host-pathogen interactions. CLINICAL TRIAL: Not applicable.

Humans↗

PubMed2005

Phenotypic and functional profiling of human proinflammatory type-1 and anti-inflammatory type-2 macrophages in response to microbial antigens and IFN-gamma- and CD40L-mediated costimulation.

Macrophages (Mphi) comprise a heterogeneous population of cells with various immune and homeostatic functions. Recently, we have described type-1 and type-2 human monocyte-derived Mphi subsets. Although both support outgrowth of intracellular mycobacteria, Mphi-1 secretes interleukin (IL)-23/IL-12 and supports T helper cell type 1 (Th1) responses, whereas Mphi-2 fails to produce IL-23/IL-12, predominantly secretes IL-10, and inhibits Th1 function. Here, we further describe the phenotypic and functional profiles of Mphi-1 and Mphi-2 in response to microbial antigens and interferon-gamma (IFN-gamma) and CD40L as costimulatory T cell back-talk signals. Activated IL-23(+)/IL-12(+) Mphi-1 secreted IL-1beta, IL-18, IL-6, and tumor necrosis factor-alpha (TNF-alpha), as well as IL-8, monocyte chemoattractant protein-1 (MCP-1), IFN-inducible protein 10 (IP-10), Mphi inflammatory protein-1beta (MIP-1beta), regulated on activation, normal T expressed and secreted (RANTES), Mphi-derived chemokine (MDC), and (low levels of) pulmonary and activation-regulated chemokine and thymus and activation-regulated chemokine (TARC), corroborating their proinflammatory function. Regardless of the stimulus, Mphi-2 maintained their IL-10(+) signature cytokine profile and produced no or relatively low levels of IL-12p40, IL-1beta, IL-6, TNF-alpha, MDC, or TARC. It is remarkable that Mphi-2 secreted high levels of IL-8, MCP-1, IP-10, MIP-1beta, and RANTES, suggesting an active role for these cells in regulating cellular immunity and homeostasis. Mphi-1 and Mphi-2 expressed similar levels of Toll-like receptor and dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin as microbial pattern recognition receptors. Mphi-2, unlike Mphi-1 but like other nonclassical Mphi described previously, expressed CD163 and down-modulated human leukocyte antigen and costimulatory molecules specifically upon activation. These findings demonstrate how Mphi-1/Mphi-2 polarization can differentially skew the host response toward pro- or anti-inflammatory immune responses, respectively. This is likely to be relevant for host-pathogen interactions in chronic bacterial infections and provides a model for dissecting pro- and anti-inflammatory cascades.

Antigens, Bacterial↗

PubMed2005

Viral strategies for evading antiviral cellular immune responses of the host.

The host invariably responds to infecting viruses by activating its innate immune system and mounting virus-specific humoral and cellular immune responses. These responses are aimed at controlling viral replication and eliminating the infecting virus from the host. However, viruses have evolved numerous strategies to counter and evade host's antiviral responses. Providing specific examples from the published literature, we discuss in this review article various strategies that viruses have developed to evade antiviral cellular responses of the host. Unraveling these viral strategies allows a better understanding of the host-pathogen interactions and their coevolution. This knowledge is important for identifying novel molecular targets for developing antiviral reagents. Finally, it may also help devise new knowledge-based strategies for developing antiviral vaccines.

Animals↗

PubMed2006

Immunomodulatory roles of the carcinoembryonic antigen family of glycoproteins.

One of the most remarkable aspects of the immune system is its ability to fashion an immune response most appropriate to the activating stimulus. Although the immune system possesses a number of adaptations to accomplish this, an important theme is local immune regulation by site-specific expression of receptors and ligands. One family of molecules that is gaining attention as modulators of the immune system is the carcinoembryonic antigen cell-adhesion molecule family (CEACAM). Functionally, the carcinoembryonic antigen family can mediate cell-cell contact, host-pathogen interactions, and immune regulation. For example, biliary glycoprotein (CEACAM1) can have direct activity on T cells, leading to the inhibition of helper or cytotoxic T cell function. The expression of carcinoembryonic antigen (CEACAM5) on intestinal epithelial cells is involved in the activation of populations of regulatory CD8(+) T cells, while a distinct subset of regulatory CD8+ T cells is activated by nonspecific cross-reacting antigen (CEACAM6) on placental trophoblasts. Interestingly, the function and phenotype of these cells depend upon the specific member of the carcinoembryonic antigen family expressed, as well as the antigen-presenting molecule with which it associates. Thus, these glycoproteins comprise a family of molecules whose functions can depend on their nature and context.

Bacterial Adhesion↗

PubMed2003

Bacterial genomes and infectious diseases.

The genome sequencing approach has proved to be highly effective and invaluable for gaining an insight on structure of bacteria genomes and the biology and evolution of bacteria. The diversity of bacteria genomes is beyond expectation. Gaining a full understanding of the biology and pathogenic mechanisms of these pathogens will be a major task because on an average only approximately 69% of the encoded proteins in each genome have known functions. Genome sequence analyses have identified novel putative virulence genes, vaccine candidates, targets for antibacterial drugs, and specific diagnostic probes. Microarray technology that makes use of the genomic sequences of human and bacterial pathogens will be a major tool for gaining full understanding of the complexity of host-pathogen interactions and mechanisms of pathogenesis.

Bacteria↗

PubMed1976

Entomopathogens: ecological manipulation of natural associations.

The control of insect pests with entomopathogens is unique, in that naturally occurring host-pathogen relations are manipulated to the benefit of man: protecting agricultural crops and forests or controlling insect vectors of disease. The isolation and identification of a virulent pathogen is the initial step in the development of a potential control agent. Production of the pathogen in adequate quantities must be possible either in vivo (insects) or in vitro (artificial medium). To insure usefulness, the pathogen must remain viable in the formulated form and after application in the field. Since inactivation rather than persistence is a problem, the pathogens must be formulated, protected, and applied to insure satisfactory pest control action. Studying the natural host--pathogen interactions will be necessary in order to manipulate the pathogen effectively, by introducing it at the most opportune time in the life cycle of the target pest. Generally, insect pathogens are more selective than conventional pesticides; this will limit their use and industrial development. Development, at least in part, by the public sector may be necessary and desirable. The most promising areas for the use of pathogens are in integrated pest management and in situations where pests have developed resistance to chemical control.

Animals↗

PubMedDate not supplied

Differentiated cultures of primary hamster tracheal airway epithelial cells.

Primary airway epithelial cell cultures can provide a faithful representation of the in vivo airway while allowing for a controlled nutrient source and isolation from other tissues or immune cells. The methods used have significant differences based on tissue source, cell isolation, culture conditions, and assessment of culture purity. We modified and optimized a method for generating tracheal epithelial cultures from Syrian golden hamsters and characterized the cultures for cell composition and function. Soon after initial plating, the epithelial cells reached a high transepithelial resistance and formed tight junctions. The cells differentiated into a heterogeneous, multicellular culture containing ciliated, secretory, and basal cells after culture at an air-liquid interface (ALI). The secretory cell populations initially consisted of MUC5AC-positive goblet cells and MUC5AC/CCSP double-positive cells, but the makeup changed to predominantly Clara cell secretory protein (CCSP)-positive Clara cells after 14 d. The ciliated cell populations differentiated rapidly after ALI, as judged by the appearance of beta tubulin IV-positive cells. The cultures produced mucus, CCSP, and trypsin-like proteases and were capable of wound repair as judged by increased expression of matrilysin. Our method provides an efficient, high-yield protocol for producing differentiated hamster tracheal epithelial cells that can be used for a variety of in vitro studies including tracheal cell differentiation, airway disease mechanisms, and pathogen-host interactions.

Animals↗

PubMedDate not supplied

Characterization of a white bass (Morone chrysops) embryonic cell line with epithelial features.

The genus Morone is an important one for U.S. aquaculture, but there has been no available cell line from this genus. We report here a cell line (the WBE line) derived from white bass embryos that has been grown for more than 80 passages over 21 mo in Dulbecco modified Eagle medium supplemented with fetal bovine serum. The WBE line showed epithelial features with positive immunohistochemical staining for cytokeratin and intercellular junctions when observed by electron microscopy. The doubling time, transformation characteristics, response to cryopreservation, and karyotype were determined. The WBE line was also tested by polymerase chain reaction to verify the species of origin and to screen for mycoplasma infection. This epithelial cell line may prove useful for the study of host-pathogen interactions that occur at the epithelial surface in this commercially important fish species.

Animals↗

PubMed2004

Segmentally variable genes: a new perspective on adaptation.

Genomic sequence variation is the hallmark of life and is key to understanding diversity and adaptation among the numerous microorganisms on earth. Analysis of the sequenced microbial genomes suggests that genes are evolving at many different rates. We have attempted to derive a new classification of genes into three broad categories: lineage-specific genes that evolve rapidly and appear unique to individual species or strains; highly conserved genes that frequently perform housekeeping functions; and partially variable genes that contain highly variable regions, at least 70 amino acids long, interspersed among well-conserved regions. The latter we term segmentally variable genes (SVGs), and we suggest that they are especially interesting targets for biochemical studies. Among these genes are ones necessary to deal with the environment, including genes involved in host-pathogen interactions, defense mechanisms, and intracellular responses to internal and environmental changes. For the most part, the detailed function of these variable regions remains unknown. We propose that they are likely to perform important binding functions responsible for protein-protein, protein-nucleic acid, or protein-small molecule interactions. Discerning their function and identifying their binding partners may offer biologists new insights into the basic mechanisms of adaptation, context-dependent evolution, and the interaction between microbes and their environment.

Acclimatization↗

PubMed2001

Novel nonantibiotic therapies for pneumonia: cytokines and host defense.

Effective host defense against bacterial infection is dependent on the activation and recruitment of phagocytic cells. The initiation, maintenance, and resolution of this inflammatory response in the setting of bacterial pneumonia is dependent on the expression of cytokines. As the complexities of the host-pathogen interaction are further dissected and unraveled, immunologic manipulation of cytokine expression will likely become an important adjuvant therapy in the treatment of serious lung infections.

Animals↗

PubMed1985

Pulmonary cell populations in the immunosuppressed patient. Bronchoalveolar lavage findings during episodes of pneumonitis.

Bronchoalveolar lavage (BAL) cell populations were determined in 47 immunosuppressed patients during episodes of pulmonary disease. Thirty six patients had AIDS and 11 had conventional causes of immunosuppression. Pulmonary disease was due to a variety of infectious and noninfectious causes and was similar in both groups. In the AIDS patients, the mean BAL cell proportions were 64.2 +/- 3.7 percent alveolar macrophages (MACS), 28.7 +/- 3.4 percent lymphocytes, 3.5 +/- 1.8 percent polymorphonuclear cells (PMN) and 1.6 +/- 0.6 percent eosinophils (EOS). The non-AIDS group had similar findings in the BAL, with 59.3 +/- 8.3 percent MACS, 34.8 +/- 7.2 percent lymphocytes, 5.5 +/- 1.7 percent PMN and 0.4 +/- 0.2 percent EOS. The most striking finding in each group was a significant increase in both the proportion and absolute number of lymphocytes compared to controls. This was in marked contrast to the peripheral blood findings of lymphopenia. There was no characteristic cell profile diagnostic of any specific pulmonary disease. There was also no direct relationship of the cells present to respiratory symptoms, roentgenographic abnormalities or survival from pulmonary disease. This study demonstrates that although there was wide individual variation in lavage findings, a local pulmonary inflammatory reaction consisting predominantly of lymphocytes occurs in the immunosuppressed host during episodes of lung disease. The significance of this lymphocyte alveolitis and the complex host pathogen interaction responsible for determining the cell populations present in the lungs of these patients requires further study.

Acquired Immunodeficiency Syndrome↗

PubMed1998

Stress symposium in Johannesburg: plants versus humans.

On 18 February 1998, a 'Stress symposium' was held at the Rand Afrikaans University (RAU) in Johannesburg, South Africa. The meeting brought together people from both the plant and the human oxidative stress field, which was exemplified by a talk entitled 'Heat shock proteins in host-pathogen interactions: plants versus humans'. There were moments when it appeared as if the main difference between plants and humans was, as sung by Julos Beaucarne, that 'the human plant is the only one to be able to water itself...'

Animals↗

PubMed2006

Preparation of intact, highly purified phagosomes from Dictyostelium.

Phagocytosis plays a fundamental role in the immune system for the defense against invading microorganisms and the clearing of apoptotic and cancerous cells. The common amoeba Dictyostelium discoideum is a recognized model for professional immune phagocytes and is now commonly used to study host-pathogen interactions. Dictyostelium is genetically and biochemically tractable and is a most versatile experimental system. The classical protocol for purifying phagosomes formed by ingestion of latex beads particles has been adapted to Dictyostelium. It was improved in yield, purity, and synchronicity, allowing isolation of milligram amounts of phagosomal proteins and lipids. This method has been used successfully to highlight membrane trafficking and phagosome maturation. Here, we present a step-by-step protocol including detailed notes necessary for ensuring access to a large number of highly synchronized phagosomes of high purity and integrity.

Animals↗

PubMed2004

Bacteria in exacerbations of chronic obstructive pulmonary disease: phenomenon or epiphenomenon?

Our understanding of the pathogenesis and consequences of acute exacerbations of chronic obstructive pulmonary disease (COPD) has increased considerably in the past decade. Several new lines of evidence support bacterial causation of approximately half of the exacerbations in COPD. Acquisition of new strains of bacterial pathogens in patients with COPD is associated with a substantial increase in risk of exacerbation. Bacterial pathogens are isolated in significant concentrations from bronchoscopic samples obtained during acute exacerbation. Neutrophilic airway inflammation is associated with isolation of bacterial pathogens from sputum. A specific immune response to the infecting strains of bacterial pathogens isolated from sputum during exacerbations has been demonstrated. Future work should strive to understand better the host-pathogen interaction that leads to an exacerbation and to develop novel therapeutic and preventive measures.

Acute Disease↗

PubMed2004

Modulation of immune responses - strategies for optimising vaccines.

Over decades, vaccination has considerably reduced the morbidity and mortality caused by infectious pathogens. Efficient vaccines conferring long-term protection have been developed despite a minimal understanding of the specific immunological mechanisms involved in this protection. Recent technological advances have provided valuable insights into host-pathogen interactions and considerably improved our knowledge of the effector and regulatory mechanisms behind the innate and adaptive immune responses. With the ability to initiate and manipulate immune responses, it is now possible to develop and optimise safe and effective vaccination strategies using a more rational approach.

Adjuvants, Immunologic↗

PubMed2003

The art of serendipity: killing of Caenorhabditis elegans by human pathogens as a model of bacterial and fungal pathogenesis.

The nematode worm, Caenorhabditis elegans, has been used to develop a facile model system of host-pathogen interactions to identify basic evolutionarily conserved pathways associated with microbial pathogenesis. The model involves the killing of Caenorhabditis elegans by a variety of human pathogens. Several virulence-related genes in a variety of pathogens previously shown to be involved in mammalian infection have also been shown to play a role in Caenorhabditis elegans killing. Screening of large numbers of microbial mutants for attenuation in a mammalian model would require thousands of mice, rats or rabbits. In contrast, the Caenorhabditis elegans model allows rapid identification of mutants in microbial genes associated with pathogenesis and then these phenotypes can be confirmed in a relevant mammalian model.

Animals↗