scholarly journals Immune Response to Yersinia Outer Proteins and Other Yersinia pestis Antigens after Experimental Plague Infection in Mice

1999 ◽  
Vol 67 (4) ◽  
pp. 1922-1928 ◽  
Author(s):  
Gretchen E. Benner ◽  
Gerard P. Andrews ◽  
W. Russell Byrne ◽  
Susan D. Strachan ◽  
Allen K. Sample ◽  
...  
Keyword(s):  
Immune Response ◽  
Yersinia Pestis ◽  
Antibiotic Treatment ◽  
Clinical Situation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Virulence Determinants ◽  
Limited Information ◽  
Treatment Regimens ◽  
V Antigen

ABSTRACT There is limited information concerning the nature and extent of the immune response to the virulence determinants ofYersinia pestis during the course of plague infection. In this study, we evaluated the humoral immune response of mice that survived lethal Y. pestis aerosol challenge after antibiotic treatment. Such a model may replicate the clinical situation in humans and indicate which virulence determinants are expressed in vivo. Immunoglobulin G enzyme-linked immunosorbent assay and immunoblotting were performed by using purified, recombinant antigens including F1, V antigen, YpkA, YopH, YopM, YopB, YopD, YopN, YopE, YopK, plasminogen activator protease (Pla), and pH 6 antigen as well as purified lipopolysaccharide. The major antigens recognized by murine convalescent sera were F1, V antigen, YopH, YopM, YopD, and Pla. Early treatment with antibiotics tended to reduce the immune response and differences between antibiotic treatment regimens were noted. These results may indicate that only some virulence factors are expressed and/or immunogenic during infection. This information may prove useful for selecting potential vaccine candidates and for developing improved serologic diagnostic assays.

scholarly journals T helper cell polarisation as a measure of the maturation of the immune response

2003 ◽  
Vol 12 (5) ◽  
pp. 285-292 ◽  
Author(s):  
Scott B. Cameron ◽  
Ellen H. Stolte ◽  
Anthony W. Chow ◽  
Huub F. J. Savelkoul
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Intracellular Cytokine Staining ◽  
T Helper Cell ◽  
Helper Cell ◽  
Enzyme Linked Immunosorbent Assay ◽  
Intracellular Cytokine ◽  
T Helper

Background:T helper cell polarisation is important under chronic immune stimulatory conditions and drives the type of the evolving immune response. Mice treated with superantigensin vivodisplay strong effects on Thsubset differentiation. The aim of the study was to detect the intrinsic capacity of T cells to polarise under variousex vivoconditions.Methods:Purified CD4+T cells obtained from superantigen-treated mice were cultured under Thpolarising conditionsin vitro. By combining intracellular cytokine staining and subsequent flow cytometric analysis with quantitative cytokine measurements in culture supernatants by enzyme-linked immunosorbent assay (ELISA), the differential Thpolarising capacity of the treatment can be detected in a qualitative and quantitative manner.Results and conclusions:BALB/c mice were shown to be biased to develop strong Th2 polarised immune responses using Th0 stimulation of purified CD4+T cells from phosphate-buffered saline-treated mice. Nevertheless, our analysis methodology convincingly showed that even in these mice, Toxic Shock Syndrome Toxin-1 treatmentin vivoresulted in a significantly stronger Th1 polarising effect than control treatment. Our results indicate that populations of Thcells can be assessed individually for their differential Th1 or Th2 maturation capacityin vivoby analysing robustin vitropolarisation cultures combined with intracellular cytokine staining and ELISA.

scholarly journals Interactions between Yersinia pestis V-antigen (LcrV) and human Toll-like receptor 2 (TLR2) in a modelled protein complex and potential mechanistic insights

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Tiandi Wei ◽  
Jing Gong ◽  
Guojing Qu ◽  
Mingyu Wang ◽  
Hai Xu
Keyword(s):  
Immune Response ◽  
Yersinia Pestis ◽  
Mechanistic Model ◽  
White Blood Cells ◽  
Dynamics Simulation ◽  
Structure Model ◽  
Toll Like Receptor ◽  
Toll Like Receptor 2 ◽  
V Antigen

Abstract Background Yersinia pestis, the etiological pathogen of plague, is capable of repressing the immune response of white blood cells to evade phagocytosis. The V-antigen (LcrV) was found to be involved in this process by binding to human Toll-like Receptor 2 (TLR2). The detailed mechanism behind this LcrV and TLR2 mediated immune response repression, however, is yet to be fully elucidated due to the lack of structural information. Results In this work, with protein structure modelling, we were able to construct a structure model of the heterotetramer of Y. pestis LcrV and human TLR2. Molecular dynamics simulation suggests the stability of this structure in aquatic environment. The LcrV model has a dumbbell-like structure with two globule domains (G1 at N-terminus and G2 away from membrane) connected with a coiled-coil linker (CCL) domain. The two horseshoe-shape TLR2 subunits form a V-shape structure, are not in direct contact with each other, and are held together by the LcrV homodimer. In this structure model, both the G1 and CCL domains are involved in the formation of LcrV homodimer, while all three domains are involved in LcrV-TLR2 binding. A mechanistic model was proposed based on this heterotetrameric structure model: The LcrV homodimer separates the TLR2 subunits to inhibit the dimerization of TLR2 and subsequent signal transfer for immune response; while LcrV could also inhibit the formation of heterodimers of TLR2 with other TLRs, and leads to immune response repression. Conclusions A heterotetrameric structure of Y. pestis LcrV and human TLR2 was modelled in this work. Analysis of this modelled structure showed its stability in aquatic environments and the role of LcrV domains and residues in protein-protein interaction. A mechanistic model for the role of LcrV in Y. pestis pathogenesis is raised based on this heterotetrameric structure model. This work provides a hypothesis of LcrV function, with which further experimental validation may elucidate the role of LcrV in human immune response repression.

scholarly journals In vitro evaluation of immunogenic properties of active dressings

2014 ◽  
Vol 27 (1) ◽  
pp. 55-60 ◽  
Author(s):  
Joanna Orlowska ◽  
Urszula Kurczewska ◽  
Katarzyna Derwinska ◽  
Wojciech Orlowski ◽  
Daria Orszulak-Michalak
Keyword(s):  
Immune Response ◽  
Wound Dressings ◽  
Enzyme Linked Immunosorbent Assay ◽  
In Vitro Evaluation ◽  
Murine Fibroblasts ◽  
The Subject ◽  
Immunogenic Properties

Abstract The aim of this study was in vitro evaluation of the level of the immune response in relation to wound dressings composed of alginate, calcium carboxymethylcellulose, and dibutyrylochitin and determination of the direction of response, which will make referring next to the results of in vivo phase possible. The subject of the experiments was to examine the commercially available, biodegradable alginate dressing, commercially available but not biodegradable dressing constructed from the sodium carboxymethylcellulose, and synthesized in house biodegradable dressing constructed of the dibutyrylchitin. To determine the direction of the immune response, the degree of secretion of pro-inflammatory interleukin (IL-1, IL-6) and antiinflammatory (IL-10) interleukin from murine fibroblasts having contact with the tested dressings (ELISA enzyme linked immunosorbent assay), was tested.

scholarly journals Peroral Ciprofloxacin Therapy Impairs the Generation of a Protective Immune Response in a Mouse Model for Salmonella enterica Serovar Typhimurium Diarrhea, while Parenteral Ceftriaxone Therapy Does Not

2012 ◽  
Vol 56 (5) ◽  
pp. 2295-2304 ◽  
Author(s):  
Kathrin Endt ◽  
Lisa Maier ◽  
Rina Käppeli ◽  
Manja Barthel ◽  
Benjamin Misselwitz ◽  
...  
Keyword(s):  
Immune Response ◽  
Mouse Model ◽  
Antibiotic Treatment ◽  
Salmonella Enterica ◽  
Adaptive Immune Response ◽  
Content Type ◽  
Fecal Shedding ◽  
Treatment Regimens ◽  
Adaptive Immune ◽  
Serovar Typhimurium

ABSTRACTNontyphoidalSalmonella(NTS) species cause self-limiting diarrhea and sometimes severe disease. Antibiotic treatment is considered only in severe cases and immune-compromised patients. The beneficial effects of antibiotic therapy and the consequences for adaptive immune responses are not well understood. We used a mouse model forSalmonelladiarrhea to assess the effects ofper ostreatment with ciprofloxacin (15 mg/kg of body weight intragastrically 2 times/day, 5 days) or parenteral ceftriaxone (50 mg/kg intraperitoneally, 5 days), two common drugs used in human patients. The therapeutic and adverse effects were assessed with respect to generation of a protective adaptive immune response, fecal pathogen excretion, and the emergence of nonsymptomatic excreters. In the mouse model, both therapies reduced disease severity and reduced the level of fecal shedding. In line with clinical data, in most animals, a rebound of pathogen gut colonization/fecal shedding was observed 2 to 12 days after the end of the treatment. Yet, levels of pathogen shedding and frequency of appearance of nonsymptomatic excreters did not differ from those for untreated controls. Moreover, mice treated intraperitoneally with ceftriaxone developed an adaptive immunity protecting the mice from enteropathy in wild-typeSalmonella entericaserovar Typhimurium challenge infections. In contrast, the mice treated intragastrically with ciprofloxacin were not protected. Thus, antibiotic treatment regimens can disrupt the adaptive immune response, but treatment regimens may be optimized in order to preserve the generation of protective immunity. It might be of interest to determine whether this also pertains to human patients. In this case, the mouse model might be a tool for further mechanistic studies.

scholarly journals Antimicrobial Photodynamic Therapy Combined With Antibiotic in the Treatment of Rats With Third-Degree Burns

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhanjuan Zhao ◽  
Jinduo Ma ◽  
Yiyi Wang ◽  
Zehua Xu ◽  
Lu Zhao ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Antibiotic Treatment ◽  
Bacterial Species ◽  
The Other ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Antimicrobial Photodynamic Therapy ◽  
Wound Tissue

Cationic porphyrin conjugate, protoporphyrin IX-methyl ethylenediamine derivative (PPIX-MED) has a potent photosensitive antibacterial effect on clinically isolated bacteria, including methicillin-resistant Staphylococcus aureus, (MRSA), Escherichia coli, and Pseudomonas aeruginosa. This study investigated (i) the PPIX-MED-mediated antimicrobial photodynamic effect on these three species in vitro and (ii) the effect of antimicrobial photodynamic therapy (aPDT) combined with the use of an antibiotic on the healing in vivo of third-degree burns of rats with the wounds infected by these bacterial species. PPIX-MED exerted a potent inhibitory effect on the growth of the three bacterial species by producing reactive oxygen species when photoactivated. PPIX-MED-mediated antimicrobial photodynamic therapy (PPIX-MED-aPDT) had high bacterial photoinactivation ability in vitro, with a minimum inhibitory concentration of 15.6 μM PPIX-MED against each of the three types of bacteria and minimum bactericidal concentrations of 31.25 μM against MRSA and E. coli and 62.5 μM against P. aeruginosa. In rats with third-degree burns infected by a mixture of these bacteria, the bactericidal efficiency of PPIX-MED–aPDT-combined-with-antibiotic treatment was higher than that of antibiotic or aPDT treatment alone. This was confirmed by analysis of viable bacterial counts in wound tissue and blood. Enzyme-linked immunosorbent assay revealed that aPDT-combined-with-antibiotic treatment resulted in an obvious reduction in tumor necrosis factor-alpha and interleukin-6 levels compared with the no-treatment control group and the other treatment groups. Immunohistochemistry revealed that the expression of basic fibroblast growth factor and CD31 (a marker of neovascularization), expressed in burn wound tissue was higher in the aPDT-combined-with-antibiotic treatment group than in the other groups. PPIX-MED–aPDT has a promising bactericidal effect both in vitro and in vivo, and PPIX-MED–aPDT-combined-with-antibiotic treatment enhanced the healing of infected third-degree burns in rats.

scholarly journals Anti-Cancer Effects of Synergistic Drug–Bacterium Combinations on Induced Breast Cancer in BALB/c Mice

Biomolecules ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 626 ◽  
Author(s):  
Menaga Subramaniam ◽  
Norhafiza M. Arshad ◽  
Kein Seong Mun ◽  
Sharan Malagobadan ◽  
Khalijah Awang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Weight ◽  
Cancer Progression ◽  
Tumor Regression ◽  
Drug Effects ◽  
Conclusive Evidence ◽  
Enzyme Linked Immunosorbent Assay ◽  
Treatment Regimens ◽  
Anti Cancer

Cancer development and progression are extremely complex due to the alteration of various genes and pathways. In most cases, multiple agents are required to control cancer progression. The purpose of this study is to investigate, using a mouse model, the synergistic interactions of anti-cancer agents, 1′-S-1′-acetoxychavicol acetate (ACA), Mycobacterium indicus pranii (MIP), and cisplatin (CDDP) in double and triple combinations to treat chemo-sensitize and immune-sensitize breast cancer. Changes in tumor volume and body weight were monitored. Organs were harvested and stained using hematoxylin–eosin for histopathological assessment. Milliplex enzyme-linked immunosorbent assay (ELISA) was performed to determine cytokine levels, while immunohistochemistry (IHC) was conducted on tumor biopsies to verify systemic drug effects. In vivo mouse models showed tumor regression with maintenance of regular body weight for all the different treatment regimens. IHC results provided conclusive evidence indicating that combination regimens were able to down-regulate nuclear factor kappa-B activation and reduce the expression of its regulated pro-inflammatory proteins. Reduction of pro-inflammatory cytokines (e.g., IL-6, TNF-α, and IFN-ɣ) levels were observed when using the triple combination, which indicated that the synergistic drug combination was able to significantly control cancer progression. In conclusion, ACA, MIP, and CDDP together serve as promising candidates for further development and for subsequent clinical trials against estrogen-sensitive breast cancer.

scholarly journals Pharmacodynamic Functions: a Multiparameter Approach to the Design of Antibiotic Treatment Regimens

2004 ◽  
Vol 48 (10) ◽  
pp. 3670-3676 ◽  
Author(s):  
Roland R. Regoes ◽  
Camilla Wiuff ◽  
Renata M. Zappala ◽  
Kim N. Garner ◽  
Fernando Baquero ◽  
...  
Keyword(s):  
Antibiotic Treatment ◽  
Quantitative Relationship ◽  
Hill Function ◽  
Treatment Regimens ◽  
Rational Development ◽  
Time Kill ◽  
The Hill ◽  
The Relationship

ABSTRACT There is a complex quantitative relationship between the concentrations of antibiotics and the growth and death rates of bacteria. Despite this complexity, in most cases only a single pharmacodynamic parameter, the MIC of the drug, is employed for the rational development of antibiotic treatment regimens. In this report, we use a mathematical model based on a Hill function—which we call the pharmacodynamic function and which is related to previously published E max models—to describe the relationship between the bacterial net growth rates and the concentrations of antibiotics of five different classes: ampicillin, ciprofloxacin, tetracycline, streptomycin, and rifampin. Using Escherichia coli O18:K1:H7, we illustrate how precise estimates of the four parameters of the pharmacodynamic function can be obtained from in vitro time-kill data. We show that, in addition to their respective MICs, these antibiotics differ in the values of the other pharmacodynamic parameters. Using a computer simulation of antibiotic treatment in vivo, we demonstrate that, as a consequence of differences in pharmacodynamic parameters, such as the steepness of the Hill function and the minimum bacterial net growth rate attained at high antibiotic concentrations, there can be profound differences in the microbiological efficacy of antibiotics with identical MICs. We discuss the clinical implications and limitations of these results.

scholarly journals Bacterial persisters in long-term infection: Emergence and fitness in a complex host environment

2020 ◽  
Vol 16 (12) ◽  
pp. e1009112
Author(s):  
Jennifer A. Bartell ◽  
David R. Cameron ◽  
Biljana Mojsoska ◽  
Janus Anders Juul Haagensen ◽  
Tacjana Pressler ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Antibiotic Treatment ◽  
High Throughput Screening ◽  
Patient Treatment ◽  
Repeated Treatment ◽  
Bacterial Survival ◽  
Treatment Regimens ◽  
Large Patient

Despite intensive antibiotic treatment, Pseudomonas aeruginosa often persists in the airways of cystic fibrosis (CF) patients for decades, and can do so without antibiotic resistance development. Using high-throughput screening assays of bacterial survival after treatment with high concentrations of ciprofloxacin, we have determined the prevalence of persisters in a large patient cohort using 460 longitudinal isolates of P. aeruginosa from 39 CF patients. Isolates were classed as high persister variants (Hip) if they regrew following antibiotic treatment in at least 75% of the experimental replicates. Strain genomic data, isolate phenotyping, and patient treatment records were integrated in a lineage-based analysis of persister formation and clinical impact. In total, 19% of the isolates were classified as Hip and Hip emergence increased over lineage colonization time within 22 Hip+ patients. Most Hip+ lineages produced multiple Hip isolates, but few Hip+ lineages were dominated by Hip. While we observed no strong signal of adaptive genetic convergence within Hip isolates, they generally emerged in parallel or following the development of ciprofloxacin resistance and slowed growth. Transient lineages were majority Hip-, while strains that persisted over a clinically diagnosed ‘eradication’ period were majority Hip+. Patients received indistinguishable treatment regimens before Hip emergence, but Hip+ patients overall were treated significantly more than Hip- patients, signaling repeated treatment failure. When subjected to in vivo-similar antibiotic dosing, a Hip isolate survived better than a non-Hip in a structured biofilm environment. In sum, the Hip phenotype appears to substantially contribute to long-term establishment of a lineage in the CF lung environment. Our results argue against the existence of a single dominant molecular mechanism underlying bacterial antibiotic persistence. We instead show that many routes, both phenotypic and genetic, are available for persister formation and consequent increases in strain fitness and treatment failure in CF airways.

Peculiarities of the course of type I allergic reactions in patients with blood diseases

2020 ◽  
pp. 40-50
Author(s):  
A. Nikitina
Keyword(s):  
Search Engines ◽  
Anaphylactic Shock ◽  
Type I ◽  
Allergic Reactions ◽  
Common Cause ◽  
Blood Diseases ◽  
Treatment Regimens ◽  
Modern Methods

Analysis of literature data presented in search engines — Elibrary, PubMed, Cochrane — concerning the risk of developing type I allergic reactions in patients with blood diseases is presented. It is shown that the most common cause of type I allergic reactions is drugs included in the treatment regimens of this category of patients. The article presents statistics on the increase in the number of drug allergies leading to cases of anaphylactic shock in patients with blood diseases. Modern methods for the diagnosis of type I allergic reactions in vivo and in vitro are considered.

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