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Results for “Host Microbial Interactions”

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PubMed2005

Innate mechanisms for Bifidobacterium lactis to activate transient pro-inflammatory host responses in intestinal epithelial cells after the colonization of germ-free rats.

Bifidobacteria comprise a dominant microbial population group in the human intestinal tract with purported beneficial health effects on the host. In this study, we characterized the molecular mechanisms for the initial interaction of probiotic Bifidobacterium lactis strain BB12 with native and intestinal epithelial cell (IEC) lines. We showed that B. lactis-monoassociated Fisher F344 rats transiently induce phosphorylation/activation of the NF-kappaB transcriptionally active subunit RelA and the mitogen-activated protein kinase (MAPK) p38 in native IEC at day 5 after initial bacterial colonization. In addition, Interleukin 6 (IL-6) gene expression was significantly increased at day 5, demonstrating the physiological relevance of transient transcription factor activation in IEC. In contrast, Bacteroides vulgatus-monoassociated Fisher rats revealed RelA but not p38 MAPK phosphorylation and failed to trigger significant IL-6 gene expression in native IEC. Moreover, we demonstrated that B. lactis triggers NF-kappaB RelA and p38 MAPK phosphorylation in IEC lines. Adenoviral delivery of mutant IKK-beta (Ad5dnIKKbeta) and inhibition of the p38 MAPK pathway through the pharmacological inhibitor SB203580 significantly blocked B. lactis-induced IL-6 gene expression in IEC, suggesting that B. lactis triggers NF-kappaB and MAPK signaling to induce gene expression in the intestinal epithelium. Regarding the mechanisms of bacteria epithelial cell cross-talk, B. lactis-induced IL-6 gene expression was completely inhibited in TLR2 deficient mouse embryogenic fibroblasts (MEF TLR2-/-) as well as TLR2DeltaTIR transfected Mode-K cells. In conclusion, we demonstrated that probiotic bacteria transiently trigger innate signal transduction and pro-inflammatory gene expression in the intestinal epithelium at early stages of bacterial colonization.

Animals↗

PubMed1986

Binding of Staphylococcus aureus by human serum spreading factor in an in vitro assay.

Human serum spreading factor, an animal cell adhesion-promoting glycoprotein, bound Staphylococcus aureus in an assay in which association of bacteria to protein-precoated microtiter wells was quantitated. Interaction of human serum spreading factor with S. aureus suggests that this protein may play a role in host defenses and in the invasiveness and pathogenicity of microbial infections.

Antibodies, Monoclonal↗

PubMed2001

How the immune system protects the host from infection.

The immune system is made up of sets of interacting cells. The first to respond in all cases are the antigen-presenting cells (APCs), which are equipped with receptors for microbial patterns. Engagement of these receptors induces co-stimulatory molecules on the surface of the APCs, and allows it to stimulate potent CD4 T-cell responses, and also CD8 T-cell responses. This in turn leads to B-cell-derived antibody responses. The entire response is controlled by suppressor T cells, as predicted many years ago by Richard Gershon.

Animals↗

PubMed1987

Parasite accessory cell interactions in murine leishmaniasis. I. Evasion and stimulus-dependent suppression of the macrophage interleukin 1 response by Leishmania donovani.

Interleukin 1 (IL 1) is a principal mediator of the host immune response to microbial challenge. Accessory cells of the monocyte-macrophage series are a major source of this cytokine and are also chronically parasitized by protozoa of the genus Leishmania. This suggests that characterization of the macrophage IL 1 response to Leishmania would increase our understanding of the regulation of host immunity to these organisms. In the present study, the macrophage IL 1 response to Leishmania donovani was examined because infections with this organism have findings consistent with parasite-specific T cell unresponsiveness. Cytokine activity was measured either by direct stimulation or by co-stimulation of thymocytes. Conditioned media from BALB/c resident peritoneal macrophages infected with amastigotes of L. donovani contained no more IL 1 than did supernatant fluids of control cells. In contrast, supernatants from cells stimulated with lipopolysaccharide or heat-killed Listeria monocytogenes had significantly increased cytokine content. Resident cells infected with L. donovani for 4 hr before being stimulated with Listeria demonstrated a suppressed IL 1 response (approximately 40% of Listeria alone) to this secondary particulate stimulus. In contrast, the secondary response of leishmania-preinfected cells to lipopolysaccharide was not affected. To examine whether accessory cell nonresponsiveness to L. donovani (with respect to IL 1) was related to the state of macrophage activation, elicited peritoneal macrophages obtained by injection of proteose peptone were also studied. These cells responded to stimulation with lipopolysaccharide and fixed Staphylococcus aureus with increases in intracellular, membrane, and secreted cytokine activities. In contrast, L. donovani failed to induce any of these activities. This was found to be the case irrespective of whether amastigotes were alive or killed or opsonized with specific antibodies. Elicited cells preinfected with Leishmania responded normally to secondary stimulation with lipopolysaccharide, but not S. aureus (64% of Staphylococcus alone). In addition, attachment and penetration of L. donovani promastigotes and their subsequent conversion to amastigotes within macrophages failed to induce IL 1 synthesis. The findings of this study indicate that L. donovani has the ability to both evade and suppress the macrophage IL 1 response. Because this monokine provides an obligatory signal during macrophage-dependent T cell activation, evasion of signal transduction for IL 1 synthesis may be related to defects in cell-mediated immunity which occur during infections with this organism.

Animals↗

PubMed2006

Protozoan encounters with Toll-like receptor signalling pathways: implications for host parasitism.

Toll-like receptors (TLRs) have emerged as a major receptor family involved in non-self recognition. They have a vital role in triggering innate immunity and orchestrate the acquired immune response during bacterial and viral infection. However, the role of TLRs during infection with protozoan pathogens is less clear. Nevertheless, our understanding of how these parasitic microorganisms engage the host TLR signalling system has now entered a phase of rapid expansion. This Review describes recent insights into how parasitic protozoans are sensed by TLR molecules, and how the TLR system itself can be targeted by these microbial pathogens for their own survival.

Animals↗

PubMed1991

Effect of metronidazole on surface properties of Bacteroides fragilis.

The effects of subinhibitory concentrations of metronidazole on the general morphology, ultrastructure and charge and hydrophobicity of Bacteroides fragilis were investigated using transmission and scanning electron microscopy, and measurements of zeta-potentials and contact angles. Metronidazole treatment induced morphological alterations in B. fragilis. Cells became filamentous and showed a significant loss of cytoplasm. The surface anionogenicity and hydrophobicity of B. fragilis were enhanced by the drug treatment. Metronidazole, by modifying B. fragilis surface properties, could alter, indirectly, interactions with host cells.

Bacteroides fragilis↗

PubMed2000

Differential host inflammatory responses to viable versus antibiotic-killed bacteria in experimental microbial sepsis.

Staphylococcus aureus killed during imipenem or ceftazidime chemotherapy in mice elicited an early release of tumor necrosis factor alpha (TNF-alpha) into the systemic circulation. This response was coincident in time with an increase in leukocyte-endothelium adhesive interactions in the microvasculature. Equivalent responses were not observed without the antibiotic treatment (imipenem or ceftazidime). Protective efficacy of the same antibiotic treatment was markedly diminished in D-galactosamine-treated mice compared to controls; e.g., it dropped from 2,000-fold to 70-fold with 4 mg of imipenem per kg given at the time of challenge. Nevertheless, protection was quantitatively restored upon concurrent administration of neutralizing anti-TNF-alpha antibody or 4 mg of dexamethasone per kg to these TNF-alpha-hypersensitive mice. Importantly, protection afforded by dexamethasone was not seen when the animals were challenged with viable organisms but without the concurrent administration of antibiotic. An early TNF-alpha response could also be demonstrated upon challenge with Escherichia coli, but in this instance, neither the timing nor the magnitude of that response was influenced by treatment with these antibiotics. We conclude from these studies that the inflammatory response to viable versus killed bacteria may differ markedly depending on the particular bacterium, host sensitivity to TNF-alpha, and possibly the Gram stain classification.

Animals↗

PubMed2026

Bridging the airway microbiome and targeted therapy in bronchiectasis: multi-omics insights, endotypes and emerging therapies.

Bronchiectasis is a heterogeneous chronic airway disease primarily driven by persistent infection, microbial dysbiosis and dysregulated host immunity. While culture-based microbiology has historically informed clinical management, advances in high-throughput sequencing and multi-omic technologies have transformed our understanding of the airway ecosystem, revealing that disease activity is shaped not only by individual pathogens, but by complex and dynamic host-microbe interactions. Despite the breadth of descriptive microbiome data, translation into clinically actionable diagnostics or therapies has been limited. Importantly, cross-sectional correlations between microbiota and inflammation do not establish cause and effect, underscoring the need to embed host-microbiome profiling within both longitudinal and interventional therapeutic trials. In this review, we critically appraise current microbial and host multi-omics research in bronchiectasis, integrating microbiome studies with host inflammatory, proteomic and immunophenotyping data. We highlight themes emerging across cohorts, including low microbial diversity, pathogen dominance, loss of commensal networks and neutrophil-driven inflammation, and discuss how these features align with biological endotypes associated with exacerbations and treatment response. Drawing on lessons from host-directed therapeutic successes, we examine translational roadblocks limiting microbiome-guided care. We further review emerging microbiome-modulating strategies such as pathogen-specific biologics, bacteriophage therapy, live biotherapeutic products, biofilm-targeting adjuncts and precision antibiotic stewardship. Finally, we propose a roadmap toward microbiome-informed precision medicine through harmonised methodologies, integration of host and microbial biomarkers into clinical trials, and embedding multi-omics pipelines within large international registries. Collectively, these advances have the potential to shift bronchiectasis research and clinical management towards rationally designed, precision medicine-driven therapeutic strategies.

Humans↗

PubMed2003

Effects of nonpathogenic bacteria on cytokine secretion by human intestinal mucosa.

OBJECTIVE: The human intestine harbors a complex microbial ecosystem, and the mucosa is the interface between the immune system and the luminal environment. The aim of this study was to elucidate whether host-bacteria interactions influence mucosal cytokine production. METHODS: Macroscopically normal colonic specimens were obtained at surgery from eight patients with neoplasm, and inflamed ileal specimens were obtained from two patients with Crohn's disease. Mucosal explants were cultured for 24 h with either nonpathogenic Escherichia coli ECOR-26, Lactobacillus casei DN-114 001, L. casei DN-114 056, L. casei ATCC-334, or Lactobacillus bulgaricus LB-10. Each study included blank wells with no bacteria. Tissue and bacteria viability were confirmed by LDH release and culture. Concentration of tumor necrosis factor (TNF)alpha, transforming growth factor beta1, interleukin (IL)-8, and IL-10 was measured in supernatants. In parallel experiments, neutralizing anti-TNFalpha antibody was added to the culture. RESULTS: Co-culture of mucosa with bacteria did not modify LDH release. Co-culture with L. casei strains significantly reduced TNFalpha release, whereas E. coli increased it. These effects were observed both in normal and inflamed mucosa. In combination studies, L. casei DN-114 001 prevented TNFalpha stimulation by E. coli. L. casei DN-114 001 also reduced IL-8 release via a TNFalpha-independent pathway. L. casei DN-114 056 or E. coli increased IL-10 release in the presence of neutralizing anti-TNFalpha. CONCLUSIONS: Nonpathogenic bacteria interact with human intestinal mucosa and can induce changes in cytokine production that are strain specific.

Aged↗

PubMed2006

Measles virus-dendritic cell interaction via SLAM inhibits innate immunity: selective signaling through TLR4 but not other TLRs mediates suppression of IL-12 synthesis.

Two hallmarks of measles virus (MV) infection are the ability of the virus to cause immunosuppression and the resultant enhanced susceptibility of the infected host to microbial insults. We investigated the effect of MV infection on the ability of dendritic cells (DCs) to induce IL-12 via toll-like receptor (TLR) signaling. When infected with MV, transgenic mice which expressed human SLAM receptor on their DCs were defective in the selective synthesis of IL-12 in DCs in response to stimulation of TLR4 signaling, but not to engagements of TLR2, 3, 7 or 9. MV suppressed TLR4-mediated IL-12 induction in DCs even in the presence of co-stimulation with another ligand for TLR2, 3, 7, or 9. While MV V and C proteins were not responsible for IL-12 inhibition, interaction of MV hemagglutinin with human SLAM facilitated the suppression. These results suggest that MV, by altering DC function, renders them unresponsive to secondary pathogens via TLR4.

Animals↗

PubMed2006

Signalling pathways and molecular interactions of NOD1 and NOD2.

The NOD (nucleotide-binding oligomerization domain) proteins NOD1 and NOD2 have important roles in innate immunity as sensors of microbial components derived from bacterial peptidoglycan. The importance of these molecules is underscored by the fact that mutations in the gene that encodes NOD2 occur in a subpopulation of patients with Crohn's disease, and NOD1 has also been shown to participate in host defence against infection with Helicobacter pylori. Here, we focus on the molecular interactions between these NOD proteins and other intracellular molecules to elucidate the mechanisms by which NOD1 and NOD2 contribute to the maintenance of mucosal homeostasis and the induction of mucosal inflammation.

Adaptor Proteins, Signal Transducing↗

PubMed2003

Prolonged application of closed in-line suction catheters increases microbial colonization of the lower respiratory tract and bacterial growth on catheter surface.

BACKGROUND: Microorganisms become attracted to polymer surfaces for a number of reasons including positive charge of biomaterial or concentration of nutrients on the biomaterial surface. Many bacteria additionally possess specific receptors for the interaction with extracellular host protein components that adhere on the biomaterial surface. Several authors suggest that application of closed in-line polypropylene suction catheters (CISC) in intubated patients for more than 24 h is safe and can reduce the costs associated with mechanical ventilation. Therefore, we evaluated the possible role of prolonged application of CISC to cause enhanced colonization of both the biomaterial and the lower respiratory tract. MATERIALS AND METHODS: The prospective, randomized study included 23 mechanically ventilated patients. The CISC tips, adjacent segments and tracheobronchial aspirates of each patient were examined for microbial growth. RESULTS: Application for 72 h significantly enhanced the microbial growth on the CISC tips and on the adjacent catheter segment. Usage for 3 days led to a significant increase in colonization in the lower respiratory tract. CONCLUSION: Normal saline instillation in conjunction with endotracheal suctioning may lead to a dispersion of microorganisms into the lower respiratory tract. More effective self-cleaning mechanisms are necessary to decontaminate the CISC surface after suctioning.

Bacteria↗

PubMed2005

Interactions among multiple genomes: tsetse, its symbionts and trypanosomes.

Insect-borne diseases exact a high public health burden and have a devastating impact on livestock and agriculture. To date, control has proved to be exceedingly difficult. One such disease that has plagued sub-Saharan Africa is caused by the protozoan African trypanosomes (Trypanosoma species) and transmitted by tsetse flies (Diptera: Glossinidae). This presentation describes the biology of the tsetse fly and its interactions with trypanosomes as well as its symbionts. Tsetse can harbor up to three distinct microbial symbionts, including two enterics (Wigglesworthia glossinidia and Sodalis glossinidius) as well as facultative Wolbachia infections, which influence host physiology. Recent investigations into the genome of the obligate symbiont Wigglesworthia have revealed characteristics indicative of its long co-evolutionary history with the tsetse host species. Comparative analysis of the commensal-like Sodalis with free-living enterics provides examples of adaptations to the host environment (physiology and ecology), reflecting genomic tailoring events during the process of transitioning into a symbiotic lifestyle. From an applied perspective, the extensive knowledge accumulated on the genomic and developmental biology of the symbionts coupled with our ability to both express foreign genes in these microbes in vitro and repopulate tsetse midguts with these engineered microbes now provides a means to interfere with the host physiological traits which contribute to vector competence promising a novel tool for disease management.

Animals↗

PubMed2005

Host epithelial interactions with Helicobacter pylori: a role for disrupted gastric barrier function in the clinical outcome of infection?

Infection of the human stomach with Helicobacter pylori may develop into gastritis, ulceration, adenocarcinoma and mucosal lymphomas. The pathogenic mechanisms that determine the clinical outcome from this microbial-epithelial interaction remain poorly understood. An increasing number of reports suggests that disruptions of epithelial barrier function may contribute to pathology and postinfectious complications in a variety of gastrointestinal infections. The aim of this review is to critically discuss the implications of H pylori persistence on gastric disease, with emphasis on the role of myosin light chain kinase, claudins and matrix metalloproteinases in gastric permeability defects, and their contribution to the development of cancer. These mechanisms and the associated signalling events may represent novel therapeutic targets to control disease processes induced by H pylori, a microbial pathogen that colonizes the stomach of over 50% of the human population.

Cell Membrane Permeability↗

PubMed2000

Amphipathic, alpha-helical antimicrobial peptides.

Gene-encoded antimicrobial peptides are an important component of host defense in animals ranging from insects to mammals. They do not target specific molecular receptors on the microbial surface, but rather assume amphipathic structures that allow them to interact directly with microbial membranes, which they can rapidly permeabilize. They are thus perceived to be one promising solution to the growing problem of microbial resistance to conventional antibiotics. A particularly abundant and widespread class of antimicrobial peptides are those with amphipathic, alpha-helical domains. Due to their relatively small size and synthetic accessibility, these peptides have been extensively studied and have generated a substantial amount of structure-activity relationship (SAR) data. In this review, alpha-helical antimicrobial peptides are considered from the point of view of six interrelated structural and physicochemical parameters that modulate their activity and specificity: sequence, size, structuring, charge, amphipathicity, and hydrophobicity. It begins by providing an overview of how these vary in peptides from different natural sources. It then analyzes how they relate to the currently accepted model for the mode of action of alpha-helical peptides, and discusses what the numerous SAR studies that have been carried out on these compounds and their analogues can tell us. A comparative analysis of the many alpha-helical, antimicrobial peptide sequences that are now available then provides further information on how these parameters are distributed and interrelated. Finally, the systematic variation of parameters in short model peptides is used to throw light on their role in antimicrobial potency and specificity. The review concludes with some considerations on the potentials and limitations for the development of alpha-helical, antimicrobial peptides as antiinfective agents.

Amino Acid Sequence↗

PubMed2004

Immunoglobulin A1 proteases: a structure-function update.

IgA1 (immunoglobulin A1) antibodies are the first line of defence against microbial pathogens such as Neisseria meningitidis and Haemophilus influenzae. However, these bacteria secrete a site-specific protease that is capable of cleaving human IgA1 and interacting with other host components. The IgA proteases are released by the type V secretion pathway, which involves translocation through two membranes and an autolytic, post-translational processing step. Results reported recently throw light on the type V secretion pathway and on the roles of the multifunctional IgA protease. The IgA1 protease-recognition sequence is present within the IgA1 hinge region as well as in the variable sequence connecting the IgA1 protease to its translocator domain. Recent results suggest that neisserial IgA1 proteases are capable of cleaving substrates lacking the classical recognition sequence. This review will cover recent advances in the IgA protease field.

Anti-Infective Agents↗

PubMed1991

T helper cell-dependent, microbial superantigen-induced murine B cell activation: polyclonal and antigen-specific antibody responses.

Microbial superantigens (SA), bound to human B cell surface MHC class II molecules, have been shown to promote direct, "cognate" interaction with SA-reactive autologous Th cells, resulting in polyclonal Ig production. To investigate the potential for microbial SA to support Th cell-dependent, Ag-specific antibody responses, we have extended our studies to the murine system. BALB/c Th cell lines (TCL), specific for either the Mycoplasma arthritis-derived SA or the Staphylococcus aureus-derived toxic shock syndrome toxin-1) were generated. These TCL cells are SA-specific, functionally noncross-reactive, and utilize distinct TCR V beta gene families. Coculture of SA-reactive TCL cells and syngeneic B cells bearing the relevant SA results in B cell proliferation and polyclonal IgM and IgG production. In contrast, Ag-specific (SRBC-specific) antibody-forming cells are only generated in cultures that also contain SRBC. Thus, microbial SA-mediated Th-B cell interactions induce both polyclonal B cell activation and provide selective help for the proliferation and/or differentiation of B cells that have encountered specific Ag. In additional studies, we determined that the in vivo administration of toxic shock syndrome toxin-1 to young, athymic (nude) BALB/c mice results in SA binding to splenic B cells, rendering these B cells effective stimulators of and targets for SA-reactive helper TCL cells. Taken together, these results demonstrate that microbial SA mediate productive Th-B cell interactions analogous to those that occur during allospecific Th-B cell interactions in vitro and GVHD in vivo. These findings are consistent with the hypothesis that microbial SA represent environmental factors that may trigger autoimmune disease in the genetically susceptible host.

Animals↗

PubMed1995

[Interaction between anti-infective agents and phagocytes].

Metchnikoff was one of the first to suggest the need for cooperation between phagocytes and therapeutic agents for the benefit of health. After the hopes raised by the discovery and the tremendous development of antimicrobials, there is now a creeping pessimism faced with the parallel evolution of resistance strategies in the microbial world. Interest has now turned to the use of immunomodulatory drugs, alone or combined with anti-infectious agents. Another tendency is based on the possibility that antimicrobials directly interfere with the host-microbe interplay. This review is aimed at summarizing our knowledge of the interactions between antimicrobial agents and the phagocyte, still a cornerstone in the natural defence system. Despite the problems inherent in the analysis and clinical relevance of effects observed in the test tube this developing area of research could provide new therapeutic solutions beyond the year 2000.

Anti-Infective Agents↗