scholarly journals Induction of Protective Immunity against Eimeria tenella, Eimeria maxima, and Eimeria acervulina Infections Using Dendritic Cell-Derived Exosomes

2012 ◽  
Vol 80 (5) ◽  
pp. 1909-1916 ◽  
Author(s):  
Emilio del Cacho ◽  
Margarita Gallego ◽  
Sung Hyen Lee ◽  
Hyun Soon Lillehoj ◽  
Joaquin Quilez ◽  
...  
Keyword(s):  
Protective Immunity ◽  
Eimeria Tenella ◽  
Feed Conversion ◽  
Intestinal Lesion ◽  
Content Type ◽  
Immune Parameters ◽  
Eimeria Maxima ◽  
Avian Coccidiosis

ABSTRACTThis study describes a novel immunization strategy against avian coccidiosis using exosomes derived fromEimeriaparasite antigen (Ag)-loaded dendritic cells (DCs). Chicken intestinal DCs were isolated and pulsedin vitrowith a mixture of sporozoite-extracted Ags fromEimeria tenella,E. maxima, andE. acervulina, and the cell-derived exosomes were isolated. Chickens were nonimmunized or immunized intramuscularly with exosomes and subsequently noninfected or coinfected withE. tenella,E. maxima, andE. acervulinaoocysts. Immune parameters compared among the nonimmunized/noninfected, nonimmunized/infected, and immunized/infected groups were the numbers of cells secreting Th1 cytokines, Th2 cytokines, interleukin-16 (IL-16), and Ag-reactive antibodiesin vitroandin vivoreadouts of protective immunity againstEimeriainfection. Cecal tonsils, Peyer's patches, and spleens of immunized and infected chickens had increased numbers of cells secreting the IL-16 and the Th1 cytokines IL-2 and gamma interferon, greater Ag-stimulated proliferative responses, and higher numbers of Ag-reactive IgG- and IgA-producing cells followingin vitrostimulation with the sporozoite Ags compared with the nonimmunized/noninfected and nonimmunized/infected controls. In contrast, the numbers of cells secreting the Th2 cytokines IL-4 and IL-10 were diminished in immunized and infected chickens compared with the nonimmunized/noninfected and the nonimmunized/infected controls. Chickens immunized with Ag-loaded exosomes and infectedin vivowithEimeriaoocysts had increased body weight gains, reduced feed conversion ratios, diminished fecal oocyst shedding, lessened intestinal lesion scores, and reduced mortality compared with the nonimmunized/infected controls. These results suggest that successful field vaccination against avian coccidiosis using exosomes derived from DCs incubated with Ags isolated fromEimeriaspecies may be possible.

scholarly journals Anti-Coccidial Effect of Rumex Nervosus Leaf Powder on Broiler Chickens Infected with Eimeria Tenella Oocyst

Animals ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 167
Author(s):  
Mohammed M. Qaid ◽  
Saud I. Al-Mufarrej ◽  
Mahmoud M. Azzam ◽  
Maged A. Al-Garadi ◽  
Hani H. Albaadani ◽  
...  
Keyword(s):  
Broiler Chickens ◽  
Well Being ◽  
Eimeria Tenella ◽  
Feed Conversion ◽  
Commercial Diet ◽  
Leaf Powder ◽  
Avian Coccidiosis ◽  
Gain Loss

Coccidiosis a huge economic burden in poultry farms where the pathogen Eimeria harms animal well-being and survival. Besides synthetic anti-coccidial drugs, natural herbs appear to be an alternative way to prevent avian coccidiosis. Rumex nervosus (RN), a phytogenic shrub, has received considerable attention in recent years due to its significant anti-microbial effects; however, limited knowledge exists about its potential anti-coccidial functions. This study was conducted to evaluate the prophylactic and therapeutic activities of RN leaf powder in broilers infected with Eimeria tenella. Infected chickens received a commercial diet containing 1, 3, or 5 g RN powder/kg diet compared to infected broilers that treated with Sacox (PC) or compared to uninfected broilers that received a commercial diet alone (NC). Results showed that RN powder significantly (p < 0.05) reduced the lesion scores and suppressed the output of oocysts per gram (OPG) in chickens’ feces. Although RN was unable to minimize the weight gain loss due to emeriosis, RN at level 1 g improved the feed conversion ratio. Therefore, RN powder, at 5 g, possesses moderate anti-coccidial effects and hence could be used to treat avian coccidiosis in field conditions; however, further studies are required to investigate, in vitro or in vivo, the anti-coccidial potential of active ingredients.

scholarly journals A Candida albicans Strain Expressing Mammalian Interleukin-17A Results in Early Control of Fungal Growth during Disseminated Infection

2015 ◽  
Vol 83 (9) ◽  
pp. 3684-3692 ◽  
Author(s):  
Anna R. Huppler ◽  
Natasha Whibley ◽  
Carol A. Woolford ◽  
Erin E. Childs ◽  
Jie He ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Fungal Growth ◽  
Antibiotic Use ◽  
Immune Defense ◽  
Indwelling Catheters ◽  
Content Type ◽  
Immune Parameters ◽  
Interleukin 17A

Candida albicansis normally a commensal fungus of the human mucosae and skin, but it causes life-threatening systemic infections in hospital settings in the face of predisposing conditions, such as indwelling catheters, abdominal surgery, or antibiotic use. Immunity toC. albicansinvolves various immune parameters, but the cytokine interleukin-17A (IL-17A) (also known as IL-17) has emerged as a centrally important mediator of immune defense against both mucosal and systemic candidiasis. Conversely, IL-17A has been suggested to enhance the virulence ofC. albicans, indicating that it may exert detrimental effects on pathogenesis. In this study, we hypothesized that aC. albicansstrain expressing IL-17A would exhibit reduced virulencein vivo. To that end, we created aCandida-optimized expression cassette encoding murine IL-17A, which was transformed into the DAY286 strain ofC. albicans.Candida-derived IL-17A was indistinguishable from murine IL-17A in terms of biological activity and detection in standard enzyme-linked immunosorbent assays (ELISAs). Expression of IL-17A did not negatively impact the growth of these strainsin vitro. Moreover, the IL-17A-expressingC. albicansstrains showed significantly reduced pathogenicity in a systemic model ofCandidainfection, mainly evident during the early stages of disease. Collectively, these findings suggest that IL-17A mitigates the virulence ofC. albicans.

scholarly journals Cathepsin G and Neutrophil Elastase Play Critical and Nonredundant Roles in Lung-Protective Immunity against Streptococcus pneumoniae in Mice

2011 ◽  
Vol 79 (12) ◽  
pp. 4893-4901 ◽  
Author(s):  
Ines Hahn ◽  
Anna Klaus ◽  
Ann-Kathrin Janze ◽  
Kathrin Steinwede ◽  
Nadine Ding ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Neutrophil Elastase ◽  
Serine Proteases ◽  
Protective Immunity ◽  
Resonance Energy ◽  
Cathepsin G ◽  
Severe Respiratory Distress ◽  
Content Type

ABSTRACTNeutrophil serine proteases cathepsin G (CG), neutrophil elastase (NE), and proteinase 3 (PR3) have recently been shown to contribute to killing ofStreptococcus pneumoniaein vitro. However, their relevance in lung-protective immunity against different serotypes ofS. pneumoniaein vivohas not been determined so far. Here, we examined the effect of CG and CG/NE deficiency on the lung host defense againstS. pneumoniaein mice. Despite similar neutrophil recruitment, both CG knockout (KO) mice and CG/NE double-KO mice infected with focal pneumonia-inducing serotype 19S. pneumoniaedemonstrated a severely impaired bacterial clearance, which was accompanied by lack of CG and NE but not PR3 proteolytic activity in recruited neutrophils, as determined using fluorescence resonance energy transfer (FRET) substrates. Moreover, both CG and CG/NE KO mice but not wild-type mice responded with increased lung permeability to infection withS. pneumoniae, resulting in severe respiratory distress and progressive mortality. Both neutrophil depletion and ablation of hematopoietic CG/NE in bone marrow chimeras abolished intra-alveolar CG and NE immunoreactivity and led to bacterial outgrowth in the lungs of mice, thereby identifying recruited neutrophils as the primary cellular source of intra-alveolar CG and NE. This is the first study showing a contribution of neutrophil-derived neutral serine proteases CG and NE to lung-protective immunity against focal pneumonia-inducing serotype 19S. pneumoniaein mice. These data may be important for the development of novel intervention strategies to improve lung-protective immune mechanisms in critically ill patients suffering from severe pneumococcal pneumonia.

scholarly journals Transgenic Eimeria tenella Expressing Profilin of Eimeria maxima Elicits Enhanced Protective Immunity and Alters Gut Microbiome of Chickens

2018 ◽  
Vol 86 (9) ◽  
Author(s):  
Xinming Tang ◽  
Jingxia Suo ◽  
Chao Li ◽  
Mengze Du ◽  
Chaoyue Wang ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Protective Immunity ◽  
Eimeria Tenella ◽  
Specific Cell ◽  
Wild Type ◽  
Vaccine Platform ◽  
Content Type ◽  
Molecular Adjuvant ◽  
Eimeria Maxima ◽  
Transgenic Parasite

ABSTRACT Coccidiosis is one of the most serious diseases of livestock and birds in the world. Vaccination with live-parasite anticoccidial vaccines with genetic manipulation improving the immunogenicity of vaccine strains would be the best means for controlling coccidiosis in breeder and layer stocks, even in fast-growing broilers. Profilin from apicomplexan parasites is the first molecularly defined ligand for Toll-like receptor 11 (TLR11) and TLR12 in mice and is a potential molecular adjuvant. Here, we constructed a transgenic Eimeria tenella line (Et-EmPro) expressing the profilin of Eimeria maxima, the most immunogenic species of chicken coccidia, and evaluated the adjuvant effects of EmPro on the immunogenicity of E. tenella. We found that immunization with the transgenic Eimeria parasites, compared with the wild type, elicited greater parasite antigen-specific cell-mediated immunity, characterized by increased numbers of interferon gamma (IFN-γ)-secreting lymphocytes. The transgenic parasite also induced better protective immunity against E. tenella challenge than the wild type. In addition, the diversity of the fecal microbiome of the birds immunized with the transgenic parasite differed from that of the microbiome of the wild-type-immunized birds, indicating interactions of Eimeria with the gut microbiome of chickens. Our results showing enhanced immunogenicity of E. tenella by use of EmPro as a molecular adjuvant derived from the most immunogenic affinis species represent a large step forward in the development of the next generation of coccidiosis vaccines using Eimeria as a vaccine platform expressing molecular adjuvants and potentially other pathogen antigens against not only coccidiosis but also other infectious diseases.

scholarly journals Exogenous Alginate Protects Staphylococcus aureus from Killing by Pseudomonas aeruginosa

2019 ◽  
Vol 202 (8) ◽  
Author(s):  
Courtney E. Price ◽  
Dustin G. Brown ◽  
Dominique H. Limoli ◽  
Vanessa V. Phelan ◽  
George A. O’Toole
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Physical Space ◽  
Late Time ◽  
Protective Effects ◽  
Content Type ◽  
Alginate Production ◽  
The Impact

ABSTRACT Cystic fibrosis (CF) patients chronically infected with both Pseudomonas aeruginosa and Staphylococcus aureus have worse health outcomes than patients who are monoinfected with either P. aeruginosa or S. aureus. We showed previously that mucoid strains of P. aeruginosa can coexist with S. aureus in vitro due to the transcriptional downregulation of several toxic exoproducts typically produced by P. aeruginosa, including siderophores, rhamnolipids, and HQNO (2-heptyl-4-hydroxyquinoline N-oxide). Here, we demonstrate that exogenous alginate protects S. aureus from P. aeruginosa in both planktonic and biofilm coculture models under a variety of nutritional conditions. S. aureus protection in the presence of exogenous alginate is due to the transcriptional downregulation of pvdA, a gene required for the production of the iron-scavenging siderophore pyoverdine as well as the downregulation of the PQS (Pseudomonas quinolone signal) (2-heptyl-3,4-dihydroxyquinoline) quorum sensing system. The impact of exogenous alginate is independent of endogenous alginate production. We further demonstrate that coculture of mucoid P. aeruginosa with nonmucoid P. aeruginosa strains can mitigate the killing of S. aureus by the nonmucoid strain of P. aeruginosa, indicating that the mechanism that we describe here may function in vivo in the context of mixed infections. Finally, we investigated a panel of mucoid clinical isolates that retain the ability to kill S. aureus at late time points and show that each strain has a unique expression profile, indicating that mucoid isolates can overcome the S. aureus-protective effects of mucoidy in a strain-specific manner. IMPORTANCE CF patients are chronically infected by polymicrobial communities. The two dominant bacterial pathogens that infect the lungs of CF patients are P. aeruginosa and S. aureus, with ∼30% of patients coinfected by both species. Such coinfected individuals have worse outcomes than monoinfected patients, and both species persist within the same physical space. A variety of host and environmental factors have been demonstrated to promote P. aeruginosa-S. aureus coexistence, despite evidence that P. aeruginosa kills S. aureus when these organisms are cocultured in vitro. Thus, a better understanding of P. aeruginosa-S. aureus interactions, particularly mechanisms by which these microorganisms are able to coexist in proximal physical space, will lead to better-informed treatments for chronic polymicrobial infections.

scholarly journals In Vitro Synergy and In Vivo Activity of Tigecycline-Ciprofloxacin Combination Therapy against Vibrio vulnificus Sepsis

2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Seong Eun Kim ◽  
Hee Kyung Kim ◽  
Su-Mi Choi ◽  
Yohan Yu ◽  
Uh Jin Kim ◽  
...  
Keyword(s):  
Survival Rate ◽  
Mortality Rate ◽  
Combination Therapy ◽  
Combination Treatment ◽  
Vibrio Vulnificus ◽  
Antibiotic Regimen ◽  
Content Type ◽  
Time Kill

ABSTRACT The mortality rate associated with Vibrio vulnificus sepsis remains high. An in vitro time-kill assay revealed synergism between tigecycline and ciprofloxacin. The survival rate was significantly higher in mice treated with tigecycline plus ciprofloxacin than in mice treated with cefotaxime plus minocycline. Thus, combination treatment with tigecycline-ciprofloxacin may be an effective novel antibiotic regimen for V. vulnificus sepsis.

scholarly journals ZN148 Is a Modular Synthetic Metallo-β-Lactamase Inhibitor That Reverses Carbapenem Resistance in Gram-Negative Pathogens In Vivo

2020 ◽  
Vol 64 (6) ◽  
Author(s):  
Ørjan Samuelsen ◽  
Ove Alexander Høgmoen Åstrand ◽  
Christopher Fröhlich ◽  
Adam Heikal ◽  
Susann Skagseth ◽  
...  
Keyword(s):  
Active Site ◽  
Therapeutic Potential ◽  
Treatment Options ◽  
Carbapenem Resistance ◽  
Functional Space ◽  
Bactericidal Effect ◽  
Gram Negative ◽  
Content Type

ABSTRACT Carbapenem-resistant Gram-negative pathogens are a critical public health threat and there is an urgent need for new treatments. Carbapenemases (β-lactamases able to inactivate carbapenems) have been identified in both serine β-lactamase (SBL) and metallo-β-lactamase (MBL) families. The recent introduction of SBL carbapenemase inhibitors has provided alternative therapeutic options. Unfortunately, there are no approved inhibitors of MBL-mediated carbapenem-resistance and treatment options for infections caused by MBL-producing Gram-negatives are limited. Here, we present ZN148, a zinc-chelating MBL-inhibitor capable of restoring the bactericidal effect of meropenem and in vitro clinical susceptibility to carbapenems in >98% of a large international collection of MBL-producing clinical Enterobacterales strains (n = 234). Moreover, ZN148 was able to potentiate the effect of meropenem against NDM-1-producing Klebsiella pneumoniae in a murine neutropenic peritonitis model. ZN148 showed no inhibition of the human zinc-containing enzyme glyoxylase II at 500 μM, and no acute toxicity was observed in an in vivo mouse model with cumulative dosages up to 128 mg/kg. Biochemical analysis showed a time-dependent inhibition of MBLs by ZN148 and removal of zinc ions from the active site. Addition of exogenous zinc after ZN148 exposure only restored MBL activity by ∼30%, suggesting an irreversible mechanism of inhibition. Mass-spectrometry and molecular modeling indicated potential oxidation of the active site Cys221 residue. Overall, these results demonstrate the therapeutic potential of a ZN148-carbapenem combination against MBL-producing Gram-negative pathogens and that ZN148 is a highly promising MBL inhibitor that is capable of operating in a functional space not presently filled by any clinically approved compound.

scholarly journals Arsenic Directly Binds to and Activates the Yeast AP-1-Like Transcription Factor Yap8

2015 ◽  
Vol 36 (6) ◽  
pp. 913-922 ◽  
Author(s):  
Nallani Vijay Kumar ◽  
Jianbo Yang ◽  
Jitesh K. Pillai ◽  
Swati Rawat ◽  
Carlos Solano ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcriptional Activation ◽  
Transcriptional Response ◽  
Transcriptional Regulator ◽  
Yeast Protein ◽  
Content Type ◽  
Arsenic Tolerance ◽  
Arsenic Sensing

The AP-1-like transcription factor Yap8 is critical for arsenic tolerance in the yeastSaccharomyces cerevisiae. However, the mechanism by which Yap8 senses the presence of arsenic and activates transcription of detoxification genes is unknown. Here we demonstrate that Yap8 directly binds to trivalent arsenite [As(III)]in vitroandin vivoand that approximately one As(III) molecule is bound per molecule of Yap8. As(III) is coordinated by three sulfur atoms in purified Yap8, and our genetic and biochemical data identify the cysteine residues that form the binding site as Cys132, Cys137, and Cys274. As(III) binding by Yap8 does not require an additional yeast protein, and Yap8 is regulated neither at the level of localization nor at the level of DNA binding. Instead, our data are consistent with a model in which a DNA-bound form of Yap8 acts directly as an As(III) sensor. Binding of As(III) to Yap8 triggers a conformational change that in turn brings about a transcriptional response. Thus, As(III) binding to Yap8 acts as a molecular switch that converts inactive Yap8 into an active transcriptional regulator. This is the first report to demonstrate how a eukaryotic protein couples arsenic sensing to transcriptional activation.

scholarly journals Surface-Engineered Dendrimeric Nanoconjugates for Macrophage-Targeted Delivery of Amphotericin B: Formulation Development andIn VitroandIn VivoEvaluation

2015 ◽  
Vol 59 (5) ◽  
pp. 2479-2487 ◽  
Author(s):  
Keerti Jain ◽  
Ashwni Kumar Verma ◽  
Prabhat Ranjan Mishra ◽  
Narendra Kumar Jain
Keyword(s):  
Drug Release ◽  
Amphotericin B ◽  
Human Erythrocytes ◽  
Antileishmanial Activity ◽  
Cell Uptake ◽  
Antiparasitic Activity ◽  
Content Type ◽  
Drug Localization

ABSTRACTThe present study aimed to develop an optimized dendrimeric delivery system for amphotericin B (AmB). Fifth-generation (5.0G) poly(propylene imine) (PPI) dendrimers were synthesized, conjugated with mannose, and characterized by use of various analytical techniques, including Fourier transform infrared spectroscopy (FTIR),1H nuclear magnetic resonance (1H-NMR) spectroscopic analysis, and atomic force microscopy (AFM). Mannose-conjugated 5.0G PPI (MPPI) dendrimers were loaded with AmB and evaluated for drug loading efficiency,in vitrodrug release profile, stability, hemolytic toxicity to human erythrocytes, cytotoxicity to and cell uptake by J774A.1 macrophage cells, antiparasitic activity against intracellularLeishmania donovaniamastigotes,in vivopharmacokinetic and biodistribution profiles, drug localization index, toxicity, and antileishmanial activity. AFM showed the nanometric size of the MPPI dendrimers, with a nearly globular architecture. The conjugate showed a good entrapment efficiency for AmB, along with pH-sensitive drug release. Highly significant reductions in toxicity toward human erythrocytes and macrophage cells, without compromising the antiparasitic activity of AmB, were observed. The dendrimeric formulation of AmB showed a significant enhancement of the parasiticidal activity of AmB toward intramacrophagicL. donovaniamastigotes. In thein vitrocell uptake studies, the formulation showed selectivity toward macrophages, with significant intracellular uptake. Further pharmacokinetic and organ distribution studies elucidated the controlled delivery behavior of the formulation. The drug localization index was found to increase significantly in macrophage-rich organs.In vivostudies showed a biocompatible behavior of MPPIA, with negligible toxicity even at higher doses, and promising antileishmanial activity. From the results, we concluded that surface-engineered dendrimers may serve as optimized delivery vehicles for AmB with enhanced activity and low or negligible toxicity.

scholarly journals Application of the 1-µsec pulsed-dye laser to the treatment of experimental cerebral vasospasm

1991 ◽  
Vol 75 (2) ◽  
pp. 271-276 ◽  
Author(s):  
Atsushi Teramura ◽  
Robert Macfarlane ◽  
Christopher J. Owen ◽  
Ralph de la Torre ◽  
Kenton W. Gregory ◽  
...  
Keyword(s):  
Cerebral Vasospasm ◽  
Basilar Artery ◽  
Laser Energy ◽  
Autologous Blood ◽  
Preliminary Investigation ◽  
Dye Laser ◽  
Pulsed Dye Laser ◽  
Content Type

✓ Laser energy of 480 nm was applied in 1-µsec pulses varying between 2.2 and 10 mJ to in vitro and in vivo models of cerebral vasospasm. First, the pulsed-dye laser was applied intravascularly via a 320-µm fiber to basilar artery segments from six dogs. The segments were mounted in a vessel-perfusion apparatus and constricted to, on average, 70% of resting diameter by superfusion with dog hemolysate. Immediate increase in basilar artery diameter occurred to a mean of 83% of control. In a second model, the basilar artery was exposed transclivally in the rabbit. In three normal animals, superfusion of the artery with rabbit hemolysate resulted in a reduction of mean vessel diameter to 81% of control. Following extravascular application of the laser, vessels returned to an average of 106% of the resting state. In six rabbits, the basilar artery was constricted by two intracisternal injections of autologous blood, 3 days apart. Two to 4 days after the second injection, the basilar artery was exposed. Extravascular laser treatment from a quartz fiber placed perpendicular to the vessel adventitia resulted in an immediate 53% average increase in caliber to an estimated 107% of control. No reconstriction was observed over a period of up to 5 hours. Morphologically, damage to the arterial wall was slight. This preliminary investigation suggests that the 1-µsec pulsed-dye laser may be of benefit in the treatment of cerebral vasospasm.

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