SEARCH · PubMed Health

Results for “host:pathogen interactions”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 253 records · Page 14Linked to original sources

PubMed2001

Retinoic acid and lipopolysaccharide act synergistically to increase prostanoid concentrations in rats in vivo.

Vitamin A and its active metabolite retinoic acid (RA) modulate host-pathogen interactions by interfering with the host immune and inflammatory response including prostaglandin (PG) biosynthesis. The effects of RA on phospholipase A(2) (PLA(2)) and cyclooxygenase (COX) isoforms in vitro are controversial, and few in vivo studies exist. We investigated the in vivo effects of RA on PG biosynthesis in the presence or absence of lipopolysaccharide (LPS) in rats. RA alone [10 mg/(kg. d) for 5 d] increased plasma and liver PG concentrations by increasing COX-1 protein expression (twofold that of control rats). RA acted synergistically with LPS to increase plasma (400-fold) and liver (15-fold) concentrations of prostaglandin E(2) (PGE(2)) and significantly, but to a lesser extent, other PG compared with RA rats, in the absence of major differences in PLA(2) expression or activity or COX-1 and COX-2 mRNA or protein expression. The RA + LPS-mediated increase in PGE(2) was significantly attenuated (97%) by aminoguanidine (AG), a relatively specific inhibitor of the inducible nitric oxide synthase (NOS2), consistent with the previously reported synergistic effect of RA and LPS on NOS2 expression and activity. In addition, RA and LPS induced the expression of the microsomal isoform of PGE synthase (mPGES). In conclusion, in vivo, RA and LPS increased PG and especially PGE(2) concentrations. The PGE(2) increase was associated with NOS2-mediated activation of COX and induction of mPGES. These results contribute to the characterization of the effects of vitamin A on the host inflammatory response.

Animals↗

PubMed2006

Seasonality and the dynamics of infectious diseases.

Seasonal variations in temperature, rainfall and resource availability are ubiquitous and can exert strong pressures on population dynamics. Infectious diseases provide some of the best-studied examples of the role of seasonality in shaping population fluctuations. In this paper, we review examples from human and wildlife disease systems to illustrate the challenges inherent in understanding the mechanisms and impacts of seasonal environmental drivers. Empirical evidence points to several biologically distinct mechanisms by which seasonality can impact host-pathogen interactions, including seasonal changes in host social behaviour and contact rates, variation in encounters with infective stages in the environment, annual pulses of host births and deaths and changes in host immune defences. Mathematical models and field observations show that the strength and mechanisms of seasonality can alter the spread and persistence of infectious diseases, and that population-level responses can range from simple annual cycles to more complex multiyear fluctuations. From an applied perspective, understanding the timing and causes of seasonality offers important insights into how parasite-host systems operate, how and when parasite control measures should be applied, and how disease risks will respond to anthropogenic climate change and altered patterns of seasonality. Finally, by focusing on well-studied examples of infectious diseases, we hope to highlight general insights that are relevant to other ecological interactions.

Animal Diseases↗

PubMed2003

Genetic control of the innate immune response.

BACKGROUND: Susceptibility to infectious diseases is directed, in part, by the interaction between the invading pathogen and host macrophages. This study examines the influence of genetic background on host-pathogen interactions, by assessing the transcriptional responses of macrophages from five inbred mouse strains to lipopolysaccharide (LPS), a major determinant of responses to gram-negative microorganisms. RESULTS: The mouse strains examined varied greatly in the number, amplitude and rate of induction of genes expressed in response to LPS. The response was attenuated in the C3H/HeJlpsd strain, which has a mutation in the LPS receptor Toll-like receptor 4 (TLR4). Variation between mouse strains allowed clustering into early (C57Bl/6J and DBA/2J) and delayed (BALB/c and C3H/ARC) transcriptional phenotypes. There was no clear correlation between gene induction patterns and variation at the Bcg locus (Slc11A1) or propensity to bias Th1 versus Th2 T cell activation responses. CONCLUSION: Macrophages from each strain responded to LPS with unique gene expression profiles. The variation apparent between genetic backgrounds provides insights into the breadth of possible inflammatory responses, and paradoxically, this divergence was used to identify a common transcriptional program that responds to TLR4 signalling, irrespective of genetic background. Our data indicates that many additional genetic loci control the nature and the extent of transcriptional responses promoted by a single pathogen-associated molecular pattern (PAMP), such as LPS.

Animals↗

PubMed2004

Use of cDNA microarrays to analyze responses to pneumococcal virulence factors.

BACKGROUND & OBJECTIVES: The complex interactions that occur between host and pathogen during bacteraemia caused by Streptococcus pneumoniae are not well understood. Upon entering the blood stream the pneumococcus intiates responses through contact with naïve monocytes and macrophages resulting in an inflammatory response. To elucidate the role of microbial virulence factors in the host response to the pneumococcus, cDNA microarray analysis was used to identify genes in THP-1 cells, a human monocytic cell line, that are responsive to pneumococcal virulence factors. METHODS: S. pneumoniae D39, a serotype 2 pneumococcus, and PLN an isogenic mutant of D39 that does not express pneumolysin were used. Gene expression profiles elicited by both wild-type and mutant were compared with that of THP-1 cells not exposed to pneumococci. Results obtained from microarray analysis were confirmed and further characterized using reverse transcriptase (RT)-PCR, real-time RT-PCR, and ELISA. RESULTS: Genes in THP-1 cells that were responsive to the pneumococcus independent of the presence of the specific virulence factor, pneumolysin, were identified. THP-1 cell genes that were differentially expressed independent of pneumolysin included the ones involved in cell-to-cell signaling and antipathogen responses. Those that were responsive to pneumolysin included genes encoding adhesion molecules, chemokines, cytokine receptors, and cell cycle and apoptosis proteins. INTERPRETATION & CONCLUSION: The global transcriptional response of naïve monocytes to contact with the pneumococcus was characterized and the utility of cDNA microarray analysis in elucidating the role of specific factors in host-pathogen interactions were demonstrated.

Cell Line↗

PubMed2005

Drosophila melanogaster S2 cells: a model system to study Chlamydia interaction with host cells.

Chlamydia spp. are major causes of important human diseases, but dissecting the host-pathogen interactions has been hampered by the lack of bacterial genetics and the difficulty in carrying out forward genetic screens in mammalian hosts. RNA interference (RNAi)-based methodologies for gene inactivation can now be easily carried out in genetically tractable model hosts, such as Drosophila melanogaster, and offer a new approach to identifying host genes required for pathogenesis. We tested whether Chlamydia trachomatis infection of D. melanogaster S2 cells recapitulated critical aspects of mammalian cell infections. As in mammalian cells, C. trachomatis entry was greatly reduced by heparin and cytochalasin D. Inclusions were formed in S2 cells, acquired Golgi-derived sphingolipids, and avoided phagolysosomal fusion. Elementary body (EB) to reticulate body (RB) differentiation was observed, however, no RB to EB development or host cell killing was observed. RNAi-mediated inactivation of Rac, a Rho GTPase recently shown to be required for C. trachomatis entry in mammalian cells, inhibits C. trachomatis infection in S2 cells. We conclude that Drosophila S2 cells faithfully mimic early events in Chlamydia host cell interactions and provides a bona fide system to systematically dissect host functions important in the pathogenesis of obligate intracellular pathogens.

Actins↗

PubMed2004

Transmission rates and adaptive evolution of pathogens in sympatric heterogeneous plant populations.

Diversification in agricultural cropping patterns is widely practised to delay the build-up of virulent races that can overcome host resistance in pathogen populations. This can lead to balanced polymorphism, but the long-term consequences of this strategy for the evolution of crop pathogen populations are still unclear. The widespread occurrence of sibling species and reproductively isolated sub-species among fungal and oomycete plant pathogens suggests that evolutionary divergence is common. This paper develops a mathematical model of host-pathogen interactions using a simple framework of two hosts to analyse the influences of sympatric host heterogeneity on the long-term evolutionary behaviour of plant pathogens. Using adaptive dynamics, which assumes that sequential mutations induce small changes in pathogen fitness, we show that evolutionary outcomes strongly depend on the shape of the trade-off curve between pathogen transmission on sympatric hosts. In particular, we determine the conditions under which the evolutionary branching of a monomorphic into a dimorphic population occurs, as well as the conditions that lead to the evolution of specialist (single host range) or generalist (multiple host range) pathogen populations.

Adaptation, Physiological↗

PubMed2005

Insights into host responses against pathogens from transcriptional profiling.

DNA microarrays have allowed us to monitor the effects of pathogens on host-cell gene expression programmes in great depth and on a broad scale. The comparison of results that have been generated by these studies is complex, and such a comparison has not previously been attempted in a systematic manner. In this review, we have collated and compared published transcriptional-profiling data from 32 studies that involved 77 different host-pathogen interactions, and have defined a common host-transcriptional-response. We outline gene expression patterns in the context of Toll-like receptor and pathogen-mediated signalling pathways, and summarize the contributions that transcriptional-profiling studies have made to our understanding of the infectious disease process.

Adaptation, Physiological↗

PubMed2006

Listeria monocytogenes: a multifaceted model.

The opportunistic intracellular pathogen Listeria monocytogenes has become a paradigm for the study of host-pathogen interactions and bacterial adaptation to mammalian hosts. Analysis of L. monocytogenes infection has provided considerable insight into how bacteria invade cells, move intracellularly, and disseminate in tissues, as well as tools to address fundamental processes in cell biology. Moreover, the vast amount of knowledge that has been gathered through in-depth comparative genomic analyses and in vivo studies makes L. monocytogenes one of the most well-studied bacterial pathogens.

Actins↗

PubMed2000

Changes in hydrolytic enzyme activities of naïve Atlantic salmon Salmo salar skin mucus due to infection with the salmon louse Lepeophtheirus salmonis and cortisol implantation.

The changes in the activities of mucus hydrolytic enzymes and plasma cortisol levels were examined following infection of Atlantic salmon Salmo salar with the salmon louse Lepeophtheirus salmonis and these changes were compared with those resulting from elevated plasma cortisol. Salmon were infected at high (Trial 1; 178 +/- 67) and low (Trial 2; 20 +/- 13) numbers of lice per fish and the activities of proteases, alkaline phosphatase, esterase and lysozyme in the mucus, as well as plasma cortisol levels were determined. At both levels of infection, there were significant increases of protease activity over time (1-way K-WANOVA; Trial 1, p = 0.004; Trial 2, p < 0.001). On several sampling days, generally on later days in the infections, the mucus protease activities of infected fish were significantly higher than control fish (Student's t-tests; p < 0.05). In addition, zymography experiments demonstrated bands of proteases at 17 to 22 kDa in the mucus of infected salmon that were absent in the mucus from non-infected fish and absent in the plasma of salmon. The intensity of these protease bands increased in the mucus over the course of both infections. However, plasma cortisol levels were elevated only in the heavily infected fish from the first trial. At high infection levels (Trial 1), alkaline phosphatase activity was higher in the mucus of infected fish at all days (t-test, p < 0.05). However, at the lower infection level (Trial 2), the mucus alkaline phosphatase activity did not differ significantly between infected and non-infected fish. Esterase and lysozyme activities were very low and did not change with time nor between non-infected and infected salmon in either challenge. Mucus enzyme activities of cortisol-implanted salmon did not change over time, nor were there any differences in activities between cortisol-implanted and control salmon. The present study demonstrates biochemical changes resulting from sea lice infection of Atlantic salmon occurring at the site of host-pathogen interaction, the mucus layer. However, the origin of these enzymes, whether host or pathogen, remains to be determined.

Alkaline Phosphatase↗

PubMed2004

Genetic models in pathogenesis.

To decipher the complexity of host-pathogen interactions the widest possible range of model hosts and of analytical methods is required. As some virulence mechanisms and certain host responses have been conserved throughout evolution, even simple organisms can be used as model hosts to help our understanding of infectious diseases. The availability of molecular genetic tools and a cooperative community of researchers are pivotal to the emergence of model systems. In this review, we first summarize the genetic screens that can be used to identify pathogen virulence factors, then we present a comparative overview of existing or emerging genetically tractable host models.

Animals↗

PubMed2005

The role of phenotypic variation in rhizosphere Pseudomonas bacteria.

Colony phase variation is a regulatory mechanism at the DNA level which usually results in high frequency, reversible switches between colonies with a different phenotype. A number of molecular mechanisms underlying phase variation are known: slipped-strand mispairing, genomic rearrangements, spontaneous mutations and epigenetic mechanisms such as differential methylation. Most examples of phenotypic variation or phase variation have been described in the context of host-pathogen interactions as mechanisms allowing pathogens to evade host immune responses. Recent reports indicate that phase variation is also relevant in competitive root colonization and biological control of phytopathogens. Many rhizospere Pseudomonas species show phenotypic variation, based on spontaneous mutation of the gacA and gacS genes. These morphological variants do not express secondary metabolites and have improved growth characteristics. The latter could contribute to efficient root colonization and success in competition, especially since (as shown for one strain) these variants were observed to revert to their wild-type form. The observation that these variants are present in rhizosphere-competent Pseudomonas bacteria suggests the existence of a conserved strategy to increase their success in the rhizosphere.

Bacterial Proteins↗

PubMed2025

Rv2741 Promotes Mycobacterium Survival by Modulating Macrophage Function via the IL-1α-MAPK Axis.

One of the primary healthcare problems in the world today is tuberculosis (TB), a chronic infectious illness brought on by Mycobacterium tuberculosis (M. tuberculosis). A distinct family of PE_PGRS proteins, encoded by the M. tuberculosis genome, has attracted more attention because of their involvement in immune evasion and bacterial pathogenicity. Nevertheless, the specific functions and mechanisms of action for the majority of PE_PGRS proteins remain largely unexplored. This study focuses on the Rv2741 (PE_PGRS47) gene, which is exclusively present in pathogenic mycobacteria. To examine the function of Rv2741 in host-pathogen interactions, we created recombinant strains of Mycobacterium smegmatis (M. smegmatis) that expressed the M. tuberculosis Rv2741 gene. IL-1α was found to be a key mediator of host response modulation by Rv2741. Rv2741 downregulates the secretion of IL-1α and inhibits the MAPK signaling pathway, particularly the p38 and ERK1/2 pathways, thereby cooperatively inhibiting macrophage autophagy and apoptosis. Meanwhile, the decrease in IL-1α secretion directly leads to changes in the cytokine secretion pattern and a reduction in nitric oxide (NO) production. This multifaceted regulatory mechanism ultimately favors the survival of M. smegmatis in macrophages. This research significantly expands our understanding of Rv2741 function, revealing its crucial role as a multifunctional virulence factor in the immune evasion of M. tuberculosis.

Interleukin-1alpha↗

PubMed1998

Biological principles of heredity of and resistance to disease.

Understanding the biological principles of disease heredity and resistance to disease is a prerequisite for the incorporation of these factors into multi-trait breeding programmes. Mutations represent an evolutionary aspect of disease. The author reviews patterns of Mendelian inheritance and possible causes of non-Mendelian inheritance, such as multifactorial inheritance, expansion of trinucleotide repeats, mitochondiral inheritance and genomic imprinting, in relation to diseases of domestic animals. Host-pathogen interactions underlie genetic variability in resistance to disease. Infectious pathogens endowed with a high potential for evolutionary change use this potential to evade various host defence mechanisms. This interaction may have a competitive or co-evolutionary character. The host immune system copes with the variability of pathogens by using the potential of genetic diversity of lymphocytes in immunoglobulin, T-cell receptor and major histocompatibility complex genes. Possible mechanisms for maintenance of this diversity are discussed in the context of selection for disease resistance.

Animals↗

PubMed2026

Genome-wide CRISPR screen reveals PEX11B as a host restriction factor against ORFV through membrane fluidity regulation.

Host-pathogen interactions are shaped by cellular restriction factors that direct antiviral defenses. We built the first ovine genome-wide CRISPR knockout library in sheep testis (OA3.Ts) cells, targeting all protein-coding genes. Using this platform, we identified PEX11B, a peroxisomal membrane regulatory protein, as a strong restriction factor against orf virus (ORFV) infection. Removing PEX11B increased viral susceptibility and triggered severe cytopathic effects with membrane fusion and syncytia formation. Mechanistic studies showed that PEX11B knockout harmed peroxisomal integrity and disrupted lipid metabolism. This led to greater plasma membrane fluidity, creating a proviral environment that allowed more viral entry and replication. These results reveal a new antiviral function for PEX11B in blocking viral infection and underscore the importance of peroxisomal regulation in host-virus interactions.

Animals↗

PubMed1999

Controlling the maturation of pathogen-containing vacuoles: a matter of life and death.

Once considered to be contained, infectious diseases of bacterial origin are now making a comeback. A lack of innovative therapies and the appearance of drug-resistant pathogens are becoming increasingly serious problems. A better understanding of pathogen-host interactions at the cellular and molecular levels is necessary to define new targets in our fight against microorganisms. In the past few years, the merging of cell biology and microbiology has started to yield critical and often surprising new information on the interactions that occur between various pathogens and their mammalian host cells. Here we focus on the intracellular routing of vacuoles containing microorganisms, as well as on the bacterial effectors and their host-cell targets that control vacuole maturation. We also describe new approaches for isolating microorganism-containing vacuoles and analysing their molecular composition, which will help researchers to define the molecules and mechanisms governing vacuole biogenesis.

Animals↗

PubMed2006

Infection in a dish: high-throughput analyses of bacterial pathogenesis.

Diverse aspects of host-pathogen interactions have been studied using non-mammalian hosts such as Dictyostelium discoideum, Caenorhabditis elegans, Drosophila melanogaster and Danio rerio for more than 20 years. Over the past two years, the use of these model hosts to dissect bacterial virulence mechanisms has been expanded to include the important human pathogens Vibrio cholerae and Yersinia pestis. Innovative approaches using these alternative hosts have also been developed, enabling the isolation of new antimicrobials through screening large libraries of compounds in a C. elegans Enterococcus faecalis infection model. Host proteins required by Mycobacterium and Listeria during their invasion and intracellular growth have been uncovered using high-throughput dsRNA screens in a Drosophila cell culture system, and immune evasion mechanisms deployed by Pseudomonas aeruginosa during its infection of flies have been identified. Together, these reports further illustrate the potential and relevance of these non-mammalian hosts for modelling many facets of bacterial infection in mammals.

Animals↗

PubMed2025

Biofilms in clinical infection: pathophysiology, diagnosis, and the evolving therapeutic landscape.

Biofilms are structured communities of microorganisms encased in a self-produced polymeric matrix that typically adhere to surfaces. Recent research, however, has revealed that non-attached aggregates share many common traits with the surface-dependent biofilms. This mode of bacterial growth provides enhanced protection against antibiotics and resistance to host immune defenses. Biofilms require higher antibiotic concentrations than those needed to inhibit planktonic bacteria, necessitating prolonged high-dose and combination therapies to achieve effective eradication. This increased resistance is attributed to multiple factors, including the protective extracellular matrix, reduced metabolic activity of bacteria within the biofilm, and also the ability of bacterial genomes to rapidly adjust in response to environmental changes. Diagnostic modalities such as sonication, tissue culture, and polymerase chain reaction-based assays currently dominate clinical diagnostics of biofilm infections due to their practicality, cost-effectiveness, and proven reliability. Recent research has led to innovative treatment strategies that target biofilm structure, enhance drug delivery, and modulate host-pathogen interactions. This review summarizes our current knowledge of biofilm formation, explores the current techniques for detecting microbial biofilms, and discusses future perspectives for advancing diagnostic and therapeutic strategies.

Biofilms↗

PubMed2000

The modulation of host cell apoptosis by intracellular bacterial pathogens.

Recent years have witnessed significant advances in unraveling the elegant mechanisms by which intracellular bacterial pathogens induce and/or block apoptosis, which can influence disease progression. This intriguing aspect of the host-pathogen interaction adds another fascinating dimension to our understanding of the exploitation of host cell biology by intracellular bacterial pathogens.

Apoptosis↗