scholarly journals Captivity and exposure to the emerging fungal pathogen Batrachochytrium salamandrivorans are linked to perturbation and dysbiosis of the amphibian skin microbiome

2018 ◽  
Author(s):  
Kieran A Bates ◽  
Jennifer MG Shelton ◽  
Victoria L Mercier ◽  
Kevin P Hopkins ◽  
Xavier A Harrison ◽  
...  
Keyword(s):  
Fungal Pathogen ◽  
Ex Situ ◽  
Amphibian Conservation ◽  
Skin Microbiome ◽  
Amphibian Skin ◽  
Triturus Cristatus ◽  
Batrachochytrium Salamandrivorans ◽  
Increased Risk ◽  
The Impact

The emerging fungal pathogen, Batrachochytrium salamandrivorans (Bsal) is responsible for the catastrophic decline of European salamanders and poses a threat to amphibians globally. The amphibian skin microbiome is strongly associated with disease outcome for several host-pathogen systems, yet its role in Bsal infection remains unresolved. In addition, many in-vivo Bsal studies to date have relied on specimens that have been kept in captivity for long periods without considering the influence of environment on the microbiome and how this may impact the host response to pathogen exposure. We characterised the impact of captivity and exposure to Bsal on the skin bacterial and fungal communities of two co-occurring European newt species, the smooth newt (Lissotriton vulgaris) and the great-crested newt (Triturus cristatus). Bsal infection and subsequent mortality in both newt species was associated with perturbation of the skin microbiome and possible dysbiosis. In addition, reduced microbial diversity and changes in microbiome structure accompanied the transition of newts from the wild to captivity, suggesting a possible decline in microbe-associated protection and increased risk of infection by opportunistic pathogens. Our findings advance current understanding of the role of host-associated microbiota in Bsal infection and highlight important considerations for ex-situ amphibian conservation programmes.

scholarly journals Captivity and Infection by the Fungal Pathogen Batrachochytrium salamandrivorans Perturb the Amphibian Skin Microbiome

2019 ◽  
Vol 10 ◽  
Author(s):  
Kieran A. Bates ◽  
Jennifer M. G. Shelton ◽  
Victoria L. Mercier ◽  
Kevin P. Hopkins ◽  
Xavier A. Harrison ◽  
...  
Keyword(s):  
Fungal Pathogen ◽  
Skin Microbiome ◽  
Amphibian Skin ◽  
Batrachochytrium Salamandrivorans

scholarly journals Active vitamin D (1,25-dihydroxyvitamin D3) increases host susceptibility toCitrobacter rodentiumby suppressing mucosal Th17 responses

2012 ◽  
Vol 303 (12) ◽  
pp. G1299-G1311 ◽  
Author(s):  
Natasha R. Ryz ◽  
Scott J. Patterson ◽  
Yiqun Zhang ◽  
Caixia Ma ◽  
Tina Huang ◽  
...  
Keyword(s):  
Vitamin D ◽  
Immune Responses ◽  
Bacterial Pathogen ◽  
Enteric Bacteria ◽  
Host Susceptibility ◽  
Active Vitamin ◽  
Active Vitamin D ◽  
Increased Risk ◽  
The Impact

Vitamin D deficiency affects more that 1 billion people worldwide and is associated with an increased risk of developing a number of inflammatory/autoimmune diseases, including inflammatory bowel disease (IBD). At present, the basis for the impact of vitamin D on IBD and mucosal immune responses is unclear; however, IBD is known to reflect exaggerated immune responses to luminal bacteria, and vitamin D has been shown to play a role in regulating bacteria-host interactions. Therefore, to test the effect of active vitamin D on host responses to enteric bacteria, we gave 1,25(OH)2D3to mice infected with the bacterial pathogen Citrobacter rodentium, an extracellular microbe that causes acute colitis characterized by a strong Th1/Th17 immune response. 1,25(OH)2D3treatment of infected mice led to increased pathogen burdens and exaggerated tissue pathology. In association with their increased susceptibility, 1,25(OH)2D3-treated mice showed substantially reduced numbers of Th17 T cells within their infected colons, whereas only modest differences were noted in Th1 and Treg numbers. In accordance with the impaired Th17 responses, 1,25(OH)2D3-treated mice showed defects in their production of the antimicrobial peptide REG3γ. Taken together, these studies show that 1,25(OH)2D3suppresses Th17 T-cell responses in vivo and impairs mucosal host defense against an enteric bacterial pathogen.

A switch toward angiostatic gene expression impairs the angiogenic properties of endothelial progenitor cells in low birth weight preterm infants

Blood ◽  
2011 ◽  
Vol 118 (6) ◽  
pp. 1699-1709 ◽  
Author(s):  
Isabelle Ligi ◽  
Stéphanie Simoncini ◽  
Edwige Tellier ◽  
Paula Frizera Vassallo ◽  
Florence Sabatier ◽  
...  
Keyword(s):  
Birth Weight ◽  
Low Birth Weight ◽  
Profile Analysis ◽  
Preterm Neonates ◽  
Akt Phosphorylation ◽  
Protein Levels ◽  
Increased Risk ◽  
The Impact

Abstract Low birth weight (LBW) is associated with increased risk of cardiovascular diseases at adulthood. Nevertheless, the impact of LBW on the endothelium is not clearly established. We investigate whether LBW alters the angiogenic properties of cord blood endothelial colony forming cells (LBW-ECFCs) in 25 preterm neonates compared with 25 term neonates (CT-ECFCs). We observed that LBW decreased the number of colonies formed by ECFCs and delayed the time of appearance of their clonal progeny. LBW dramatically reduced LBW-ECFC capacity to form sprouts and tubes, to migrate and to proliferate in vitro. The angiogenic defect of LBW-ECFCs was confirmed in vivo by their inability to form robust capillary networks in Matrigel plugs injected in nu/nu mice. Gene profile analysis of LBW-ECFCs demonstrated an increased expression of antiangiogenic genes. Among them, thrombospondin 1 (THBS1) was highly expressed at RNA and protein levels in LBW-ECFCs. Silencing THBS1 restored the angiogenic properties of LBW-ECFCs by increasing AKT phosphorylation. The imbalance toward an angiostatic state provide a mechanistic link between LBW and the impaired angiogenic properties of ECFCs and allows the identification of THBS1 as a novel player in LBW-ECFC defect, opening new perspectives for novel deprogramming agents.

scholarly journals Clinical and naturalistic substrates differ in bacterial communities and in their effects on skin microbiota in captive fire salamanders (Salamandra salamandra)

2020 ◽  
pp. 10-16
Author(s):  
Christopher Michaels
Keyword(s):  
Bacterial Communities ◽  
Hybrid Approach ◽  
Ex Situ ◽  
Skin Microbiota ◽  
Advantages And Disadvantages ◽  
Clinical Paper ◽  
Batrachochytrium Salamandrivorans ◽  
Salamandra Salamandra ◽  
The Impact ◽  
Paper Towels

The fire salamander (Salamandra salamandra and its relatives) is of increasing priority for ex situ conservation due to the spread of the fungal pathogen Batrachochytrium salamandrivorans in Europe. In captivity, the species may be maintained on a clinical paper-based or a naturalistic substrate, either of which has its own advantages and disadvantages. However, the impact of these two substrates on bacterial microbiotas within an enclosure and on the salamanders themselves is unknown. To investigate this, we maintained captive fire salamanders on either paper towels or a naturalistic substrate and quantified the culturable microbiotas of both substrates across the one-week lifespan of a paper towel and of the salamanders themselves over a six-month period. We found significant differences in the bacterial communities associated with the two substrates. Over a week-long period, there were major fluctuations in the community composition and abundance on paper towels while on the naturalistic substrate bacterial communities were relatively stable. The skin microbiota of salamanders were indistinguishable at the beginning of the study but after six months differed significantly between the two treatments, although the bacterial morphotypes present remained relatively similar compared with changes between substrates. These data show that husbandry protocols may have a strong influence on the culturable bacterial communities to which captive amphibians are exposed. Nevertheless, the animals were apparently able to maintain their own microbiota to a considerable degree. These findings should be borne in mind when determining husbandry protocols. Given the relative benefits of both types of enclosure, it is possible that a hybrid approach could be used whereby a small amount of naturalistic substrate is provided in a container within an otherwise clinical enclosure, to act as a bacterial reservoir.

scholarly journals BM is preferred over PBSCs in transplantation from an HLA-matched related female donor to a male recipient

2019 ◽  
Vol 3 (11) ◽  
pp. 1750-1760 ◽  
Author(s):  
Hideki Nakasone ◽  
Koji Kawamura ◽  
Kimikazu Yakushijin ◽  
Akihito Shinohara ◽  
Masatsugu Tanaka ◽  
...  
Keyword(s):  
Hematopoietic Cell Transplantation ◽  
Peripheral Blood Stem Cells ◽  
Increased Risk ◽  
Blood Stem Cells ◽  
Female Donor ◽  
Related Donor ◽  
Male Patients ◽  
The Impact ◽  
Standard Risk

Abstract The use of granulocyte colony-stimulating factor–mobilized peripheral blood stem cells (PBSCs) and sex-mismatched hematopoietic cell transplantation (HCT), especially with female donors and male recipients (FtoM), is known to be associated with an increased risk of chronic graft-versus-host disease (GVHD) compared with transplantation with bone marrow (BM). This raises the question of whether the use of PBSCs in FtoM HCT might affect allogeneic responses, resulting in fatal complications. Using a Japanese transplantation registry database, we analyzed 1132 patients (FtoM, n = 315; MtoF, n = 260; sex-matched, n = 557) with standard-risk diseases who underwent HCT with an HLA-matched related donor without in vivo T-cell depletion between 2013 and 2016. The impact of PBSC vs BM on transplantation outcomes was separately assessed in FtoM, MtoF, and sex-matched HCT. Overall survival (OS) and nonrelapse mortality (NRM) at 2 years post-HCT were significantly worse in patients with PBSCs vs those with BM in FtoM HCT (2-year OS, 76% vs 62%; P = .0084; 2-year NRM, 10% vs 21%; P = .0078); no differences were observed for MtoF or sex-matched HCT. Multivariate analyses confirmed the adverse impact of PBSCs in FtoM HCT (hazard ratio [HR] for OS, 1.91; P = .025; HR for NRM, 3.70; P = .0065). In FtoM HCT, patients with PBSCs frequently experienced fatal GVHD and organ failure. In conclusion, the use of PBSCs in FtoM HCT was associated with an increased risk of NRM in the early phase, resulting in inferior survival. This suggests that, when we use female-related donors for male patients in HCT, BM may result in better outcomes than PBSCs.

Abstract 100: HIV Protein Tat Induces Macrophage Dysfunction and Atherosclerosis Development in LDLR-deficient Mice

2020 ◽  
Vol 40 (Suppl_1) ◽  
Author(s):  
Zhaojie Meng ◽  
Weiwei Lu ◽  
Taesik Gwag ◽  
Changcheng Zhou
Keyword(s):  
Inflammatory Responses ◽  
Atherosclerotic Lesion ◽  
Iκb Kinase ◽  
Increased Risk ◽  
Macrophage Dysfunction ◽  
Atherosclerosis Development ◽  
And Migration ◽  
The Impact ◽  
Hiv 1

Introduction: As the average lifespan of HIV-infected patients receiving anti-retroviral therapy lengthens, morbidity and mortality from cardiovascular disease pose considerable challenges. HIV infection is consistently associated with increased risk of atherosclerosis development, but the underlying mechanisms remain elusive. HIV-1 Tat protein, a transcriptional activator of HIV virus, has been shown to activate NF-κB signaling and promote inflammation in vitro. However, the atherogenic effects of HIV-1 Tat have not been investigated in vivo. Macrophage is one of the major cell types involved in the initiation and progression of atherosclerosis. We and others have previously demonstrated that NF-κB signaling functions in macrophages to regulate atherogenesis. This study aims to investigate the impact of HIV-1 Tat exposure on macrophage functions and atherogenesis. Hypothesis: HIV-1 Tat activates IκB kinase β (IKKβ), a central coordinator in inflammation through activation of NF-κB, to induce macrophage dysfunction and atherosclerosis development. Methods: To investigate the effects of HIV-1 Tat on macrophage IKKβ signaling and atherosclerosis development in vivo, myeloid-specific IKKβ-deficient LDLR-deficient (IKKβ ΔMye LDLR -/- ) mice and their control littermates (IKKβ F/F LDLR -/- ) were exposed to recombinant HIV-1 Tat for 12 weeks. The effects of HIV-1 Tat on macrophage functions including inflammatory responses, adhesion and migration properties were also studied. Results and Conclusions: HIV-1 Tat significantly increased atherosclerotic lesion size in aortic root and brachiocephalic artery of IKKβ F/F LDLR -/- but not IKKβ ΔMye LDLR -/- mice. Deficiency of myeloid IKKβ attenuated macrophage inflammatory responses and decreased atherosclerotic lesional inflammation in IKKβ ΔMye LDLR -/- mice. In addition, HIV-1 Tat stimulated adhesion and migration properties of control macrophages but had no effects on IKKβ-deficient macrophages. In conclusion, our findings reveal the atherogenic effects of HIV-1 Tat in vivo and demonstrate a pivot role of myeloid IKKβ in HIV-1 Tat-driven atherogenesis.

scholarly journals Behaviour of Titanium Dioxide Particles in Artificial Body Fluids and Human Blood Plasma

2021 ◽  
Vol 22 (19) ◽  
pp. 10614
Author(s):  
Eva Korábková ◽  
Věra Kašpárková ◽  
Daniela Jasenská ◽  
Dita Moricová ◽  
Eliška Daďová ◽  
...  
Keyword(s):  
Blood Plasma ◽  
Human Blood ◽  
Body Fluids ◽  
Human Blood Plasma ◽  
Tio2 Particles ◽  
Commercial Mixture ◽  
Increased Risk ◽  
The Impact

The growing application of materials containing TiO2 particles has led to an increased risk of human exposure, while a gap in knowledge about the possible adverse effects of TiO2 still exists. In this work, TiO2 particles of rutile, anatase, and their commercial mixture were exposed to various environments, including simulated gastric fluids and human blood plasma (both representing in vivo conditions), and media used in in vitro experiments. Simulated body fluids of different compositions, ionic strengths, and pH were used, and the impact of the absence or presence of chosen enzymes was investigated. The physicochemical properties and agglomeration of TiO2 in these media were determined. The time dependent agglomeration of TiO2 related to the type of TiO2, and mainly to the type and composition of the environment that was observed. The presence of enzymes either prevented or promoted TiO2 agglomeration. TiO2 was also observed to exhibit concentration-dependent cytotoxicity. This knowledge about TiO2 behavior in all the abovementioned environments is critical when TiO2 safety is considered, especially with respect to the significant impact of the presence of proteins and size-related cytotoxicity.

scholarly journals In-vivo impact of common cosmetic preservative systems in full formulation on the skin microbiome

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254172
Author(s):  
Barry Murphy ◽  
Michael Hoptroff ◽  
David Arnold ◽  
Richard Eccles ◽  
Stuart Campbell-Lee
Keyword(s):  
Essential Role ◽  
Microbial Contamination ◽  
Skin Microbiome ◽  
Cosmetic Formulations ◽  
Microbial Contaminants ◽  
Potential Impact ◽  
The Impact ◽  
Growth Of Bacteria

Preservatives play an essentially role in ensuring that cosmetic formulations remain safe for use via control of microbial contamination. Commonly used preservatives include organic acids, alcohols and phenols and these play an essential role in controlling the growth of bacteria, fungi and moulds in substrates that can potentially act as a rich food source for microbial contaminants. Whilst the activity of these compounds is clear, both in vitro and in formulation, little information exists on the potential impact that common preservative systems, in full formulation, have on the skin’s resident microbiome. Dysbiosis of the skin’s microbiome has been associated with a number of cosmetic conditions but there currently are no in vivo studies investigating the potential for preservative ingredients, when included in personal care formulations under normal use conditions, to impact the cutaneous microbiome. Here we present an analysis of four in vivo studies that examine the impact of different preservation systems in full formulation, in different products formats, with varying durations of application. This work demonstrates that despite the antimicrobial efficacy of the preservatives in vitro, the skin microbiome is not impacted by preservative containing products in vivo.

An ACE inhibitor reduces bactericidal activity of human neutrophils in vitro and impairs mouse neutrophil activity in vivo

2021 ◽  
Vol 13 (604) ◽  
pp. eabj2138
Author(s):  
Duo-Yao Cao ◽  
Jorge F. Giani ◽  
Luciana C. Veiras ◽  
Ellen A. Bernstein ◽  
Derick Okwan-Duodu ◽  
...  
Keyword(s):  
Bactericidal Activity ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Leukotriene B4 ◽  
Human Neutrophils ◽  
Converting Enzyme Inhibitors ◽  
Bacterial Killing ◽  
Increased Risk ◽  
The Impact

Angiotensin-converting enzyme inhibitors (ACEIs) are used by millions of patients to treat hypertension, diabetic kidney disease, and heart failure. However, these patients are often at increased risk of infection. To evaluate the impact of ACEIs on immune responses to infection, we compared the effect of an ACEI versus an angiotensin receptor blocker (ARB) on neutrophil antibacterial activity. ACEI exposure reduced the ability of murine neutrophils to kill methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Klebsiella pneumoniae in vitro. In vivo, ACEI-treated mice infected with MRSA had increased bacteremia and tissue bacteria counts compared to mice treated with an ARB or with no drug. Similarly, ACEIs, but not ARBs, increased the incidence of MRSA-induced infective endocarditis in mice with aortic valve injury. Neutrophils from ACE knockout (KO) mice or mice treated with an ACEI produced less leukotriene B4 (LTB4) upon stimulation with MRSA or lipopolysaccharide, whereas neutrophils overexpressing ACE produced more LTB4 compared to wild-type neutrophils. As a result of reduced LTB4 production, ACE KO neutrophils showed decreased survival signaling and increased apoptosis. In contrast, neutrophils overexpressing ACE had an enhanced survival phenotype. Last, in a cohort of human volunteers receiving the ACEI ramipril for 1 week, ACEI administration reduced neutrophil superoxide and reactive oxygen species production and neutrophils isolated from volunteers during ramipril treatment had reduced bactericidal activity. Together, these data demonstrate that ACEI treatment, but not ARB treatment, can reduce the bacterial killing ability of neutrophils.

scholarly journals The Lung Mucosa Environment in the Elderly Increases Host Susceptibility to Mycobacterium tuberculosis Infection

2019 ◽  
Vol 220 (3) ◽  
pp. 514-523 ◽  
Author(s):  
Juan I Moliva ◽  
Michael A Duncan ◽  
Angélica Olmo-Fontánez ◽  
Anwari Akhter ◽  
Eusondia Arnett ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
The Elderly ◽  
Surfactant Protein ◽  
Host Susceptibility ◽  
Surfactant Protein D ◽  
Mycobacterium Tuberculosis Infection ◽  
Increased Risk ◽  
The Impact

AbstractAs we age, there is an increased risk for the development of tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) infection. Few studies consider that age-associated changes in the alveolar lining fluid (ALF) may increase susceptibility by altering soluble mediators of innate immunity. We assessed the impact of adult or elderly human ALF during Mtb infection in vitro and in vivo. We identified amplification of pro-oxidative and proinflammatory pathways in elderly ALF and decreased binding capability of surfactant-associated surfactant protein A (SP-A) and surfactant protein D (SP-D) to Mtb. Human macrophages infected with elderly ALF–exposed Mtb had reduced control and fewer phagosome–lysosome fusion events, which was reversed when elderly ALF was replenished with functional SP-A/SP-D. In vivo, exposure to elderly ALF exacerbated Mtb infection in young mice. Our studies demonstrate how the pulmonary environment changes as we age and suggest that Mtb may benefit from declining host defenses in the lung mucosa of the elderly.

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