scholarly journals Leishmania donovani metacyclic promastigotes impair phagosome properties in inflammatory monocytes

2021 ◽  
Author(s):  
Christine Matte ◽  
Guillermo Arango Duque ◽  
Albert Descoteaux
Keyword(s):  
Nadph Oxidase ◽  
Leishmania Donovani ◽  
Parasitophorous Vacuole ◽  
Clinical Manifestations ◽  
Parasite Burden ◽  
Surface Coat ◽  
Self Healing ◽  
Inflammatory Monocytes ◽  
Metacyclic Promastigotes ◽  
The Impact

Leishmaniasis, a debilitating disease with clinical manifestations ranging from self-healing ulcers to life-threatening visceral pathologies, is caused by protozoan parasites of the Leishmania genus. These professional vacuolar pathogens are transmitted by infected sand flies to mammalian hosts as metacyclic promastigotes and are rapidly internalized by various phagocyte populations. Classical monocytes are among the first myeloid cells to migrate to infection sites. Recent evidence shows that recruitment of these cells contributes to parasite burden and to the establishment of chronic disease. However, the nature of Leishmania-inflammatory monocyte interactions during the early stages of host infection has not been well investigated. Here, we aimed to assess the impact of Leishmania donovani metacyclic promastigotes on antimicrobial responses within these cells. Our data showed that inflammatory monocytes were readily colonized by L. donovani metacyclic promastigotes, while infection with Escherichia coli was efficiently cleared. Upon internalization, metacyclic promastigotes inhibited superoxide production at the parasitophorous vacuole (PV) through a mechanism involving exclusion of NADPH oxidase subunits gp91 phox and p47phox from the PV membrane. Moreover, we observed that unlike phagosomes enclosing zymosan particles, vacuoles containing parasites acidified poorly. Interestingly, whereas the parasite surface coat virulence glycolipid lipophosphoglycan was responsible for the inhibition of PV acidification, impairement of the NADPH oxidase assembly was independent of lipophosphoglycan and of the metalloprotease GP63. Collectively, these observations indicate that permissiveness of inflammatory monocytes to L. donovani may thus be related to the ability of this parasite to impair the microbicidal properties of phagosomes.

scholarly journals Leishmania donovani metacyclic promastigotes impair phagosome properties in inflammatory monocytes

2021 ◽  
Author(s):  
Christine Matte ◽  
Guillermo Arango Duque ◽  
Albert Descoteaux
Keyword(s):  
Nadph Oxidase ◽  
Leishmania Donovani ◽  
Parasitophorous Vacuole ◽  
Clinical Manifestations ◽  
Parasite Burden ◽  
Surface Coat ◽  
Self Healing ◽  
Inflammatory Monocytes ◽  
Metacyclic Promastigotes ◽  
The Impact

Leishmaniasis, a debilitating disease with clinical manifestations ranging from self-healing ulcers to life-threatening visceral pathologies, is caused by protozoan parasites of the Leishmania genus. These professional vacuolar pathogens are transmitted by infected sand flies to mammalian hosts as metacyclic promastigotes and are rapidly internalized by various phagocyte populations. Classical monocytes are among the first myeloid cells to migrate to infection sites. Recent evidence shows that recruitment of these cells contributes to parasite burden and to the establishment of chronic disease. However, the nature of Leishmania-inflammatory monocyte interactions during the early stages of host infection has not been well investigated. Here, we aimed to assess the impact of Leishmania donovani metacyclic promastigotes on antimicrobial responses within these cells. Our data showed that inflammatory monocytes are readily colonized by L. donovani metacyclic promastigotes, while infection with Escherichia coli is efficiently cleared. Upon internalization, metacyclic promastigotes inhibited superoxide production at the parasitophorous vacuole (PV) through a mechanism involving exclusion of NADPH oxidase subunits gp91phox and p47phox from the PV membrane. Moreover, we observed that unlike phagosomes enclosing zymosan particles, vacuoles containing parasites acidify poorly. Interestingly, whereas the parasite surface coat virulence glycolipid lipophosphoglycan (LPG) was responsible for the inhibition of PV acidification, impairment of the NADPH oxidase assembly was independent of LPG and GP63. Collectively, these observations indicate that permissiveness of inflammatory monocytes to L. donovani may thus be related to the ability of this parasite to impair the microbicidal properties of phagosomes.

scholarly journals Hematological consequences of malaria infection in mice previously treated for visceral leishmaniasis

2021 ◽  
Vol 6 ◽  
pp. 83
Author(s):  
Gulab Fatima Rani ◽  
Helen Ashwin ◽  
Najmeeyah Brown ◽  
Ian S. Hitchcock ◽  
Paul M. Kaye
Keyword(s):  
Leishmania Donovani ◽  
Severe Disease ◽  
Parasite Burden ◽  
Subsequent Development ◽  
Blood Parameters ◽  
Inos Expression ◽  
Infection Model ◽  
Clinical Responses ◽  
Previously Treated ◽  
The Impact

Background: Polyparasitism is commonplace in countries where endemicity for multiple parasites exists, and studies in animal models of coinfection have made significant inroads into understanding the impact of often competing demands on the immune system. However, few studies have addressed how previous exposure to and treatment for one infection impacts a subsequent heterologous infection.   Methods: We used a C57BL/6 mouse model of drug-treated Leishmania donovani infection followed by experimental Plasmodium chabaudi AS malaria, focusing on hematological dysfunction as a common attribute of both infections. We measured parasite burden, blood parameters associated with anemia and thrombocytopenia, and serum thrombopoietin. In addition, we quantified macrophage iNOS expression through immunohistological analysis of the liver and spleen.   Results: We found that the thrombocytopenia and anemia that accompanies primary L. donovani infection was rapidly reversed following single dose AmBisome® treatment, along with multiple other markers associated with immune activation (including restoration of tissue microarchitecture and reduced macrophage iNOS expression). Compared to naive mice, mice cured of previous VL showed comparable albeit delayed clinical responses (including peak parasitemia and anemia) to P. chabaudi AS infection. Thrombocytopenia was also evident in these sequentially infected mice, consistent with a decrease in circulating levels of thrombopoietin. Architectural changes to the spleen were also comparable in sequentially infected mice compared to those with malaria alone. Conclusions: Our data suggest that in this sequential infection model, previously-treated VL has limited impact on the subsequent development of malaria, but this issue deserves further attention in models of more severe disease or through longitudinal population studies in humans.

scholarly journals Hematological consequences of malaria in mice previously treated for visceral leishmaniasis

2021 ◽  
Vol 6 ◽  
pp. 83
Author(s):  
Gulab Fatima Rani ◽  
Helen Ashwin ◽  
Najmeeyah Brown ◽  
Ian S. Hitchcock ◽  
Paul M. Kaye
Keyword(s):  
Leishmania Donovani ◽  
Severe Disease ◽  
Parasite Burden ◽  
Subsequent Development ◽  
Blood Parameters ◽  
Inos Expression ◽  
Infection Model ◽  
Plasmodium Infection ◽  
Previously Treated ◽  
The Impact

Background: Polyparasitism is commonplace in countries where endemicity for multiple parasites exists, and studies in animal models of coinfection have made significant inroads into understanding the impact of often competing demands on the immune system. However, few studies have addressed how previous exposure to and treatment for one infection impacts a subsequent heterologous infection.   Methods: We used a C57BL/6 mouse model of drug-treated Leishmania donovani infection followed by experimental Plasmodium chabaudi AS malaria, focusing on hematological dysfunction as a common attribute of both infections. We measured parasite burden, blood parameters associated with anemia and thrombocytopenia, and serum thrombopoietin. In addition, we quantified macrophage iNOS expression through immunohistological analysis of the liver and spleen.   Results: We found that the thrombocytopenia and anemia that accompanies primary L. donovani infection was rapidly reversed following single dose AmBisome® treatment, along with multiple other markers associated with immune activation (including restoration of tissue microarchitecture and reduced macrophage iNOS expression). Compared to naive mice, mice cured of previous L. donovani infection showed comparable albeit delayed clinical responses (including peak parasitemia and anemia) to P. chabaudi AS infection. Thrombocytopenia was also evident in these sequentially infected mice, consistent with a decrease in circulating levels of thrombopoietin. Architectural changes to the spleen were also comparable in sequentially infected mice compared to those with Plasmodium infection alone. Conclusions: Our data suggest that in this sequential infection model, previously-treated L. donovani infection has limited impact on the subsequent development of Plasmodium infection, but this issue deserves further attention in models of more severe disease or through longitudinal population studies in humans.

scholarly journals Impact of rs2414096 polymorphism of CYP19 gene on susceptibility of polycystic ovary syndrome and hyperandrogenism in Kashmiri women

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sairish Ashraf ◽  
Shayaq Ul Abeer Rasool ◽  
Mudasar Nabi ◽  
Mohd Ashraf Ganie ◽  
Shariq R. Masoodi ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Clinical Manifestations ◽  
Additive Model ◽  
Genotypic Frequency ◽  
Ovary Syndrome ◽  
Significant Difference ◽  
Cyp19 Gene ◽  
Reproductive Endocrine ◽  
The Impact

AbstractPolycystic ovary syndrome (PCOS) is the most common reproductive endocrine disorder in pre-menopausal women having complex pathophysiology. Several candidate genes have been shown to have association with PCOS. CYP19 gene encodes a key steroidogenic enzyme involved in conversion of androgens into estrogens. Previous studies have reported contradictory results with regard to association of SNP rs2414096 in CYP19 gene with PCOS and hyperandrogenism in different ethnic populations. Present study was aimed to investigate the impact of SNP rs2414096 polymorphism of CYP19 gene on susceptibility of PCOS and hyperandrogenism in Kashmiri women. Further we also studied the genotypic-phenotypic association for various clinical and biochemical parameters of this polymorphism. Case control study. 394 PCOS cases diagnosed on the basis of Rotterdam criteria and age matched 306 healthy women. We found a significant differences in genotypic frequency (χ2 = 18.91, p < 0.05) as well as allele frequency (OR 0.63, CI 0.51–0.78, χ2 = 17.66, p < 0.05) between PCOS women and controls. The genotype–phenotype correlation analysis showed a significant difference in FG score (p = 0.047) and alopecia (p = 0.045) between the three genotypes. Also, the androgen excess markers like DHEAS (p < 0.001), Androstenedione (p < 0.001), Testosterone (p < 0.001) and FAI (p = 0.005) were significantly elevated in GG genotype and showed a significant difference in additive model in PCOS women. rs2414096 polymorphism of CYP19 gene is associated with the risk of PCOS as well as with clinical and biochemical markers of hyperandrogenism, hence suggesting its role in clinical manifestations of PCOS in Kashmiri women.

scholarly journals The Effect of Superabsorbent Polymers on the Microstructure and Self-Healing Properties of Cementitious-Based Composite Materials

2021 ◽  
Vol 11 (2) ◽  
pp. 700
Author(s):  
Irene A. Kanellopoulou ◽  
Ioannis A. Kartsonakis ◽  
Costas A. Charitidis
Keyword(s):  
Mechanical Properties ◽  
Composite Materials ◽  
Hybrid Structure ◽  
The Self ◽  
Self Healing ◽  
Cementitious Composite ◽  
Superabsorbent Polymers ◽  
Porosity Reduction ◽  
Environment Control ◽  
The Impact

Cementitious structures have prevailed worldwide and are expected to exhibit further growth in the future. Nevertheless, cement cracking is an issue that needs to be addressed in order to enhance structure durability and sustainability especially when exposed to aggressive environments. The purpose of this work was to examine the impact of the Superabsorbent Polymers (SAPs) incorporation into cementitious composite materials (mortars) with respect to their structure (hybrid structure consisting of organic core—inorganic shell) and evaluate the microstructure and self-healing properties of the obtained mortars. The applied SAPs were tailored to maintain their functionality in the cementitious environment. Control and mortar/SAPs specimens with two different SAPs concentrations (1 and 2% bwoc) were molded and their mechanical properties were determined according to EN 196-1, while their microstructure and self-healing behavior were evaluated via microCT. Compressive strength, a key property for mortars, which often degrades with SAPs incorporation, in this work, practically remained intact for all specimens. This is coherent with the porosity reduction and the narrower range of pore size distribution for the mortar/SAPs specimens as determined via microCT. Moreover, the self-healing behavior of mortar-SAPs specimens was enhanced up to 60% compared to control specimens. Conclusively, the overall SAPs functionality in cementitious-based materials was optimized.

scholarly journals A sand fly salivary protein acts as a neutrophil chemoattractant

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Anderson B. Guimaraes-Costa ◽  
John P. Shannon ◽  
Ingrid Waclawiak ◽  
Jullyanna Oliveira ◽  
Claudio Meneses ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Calcium Influx ◽  
Parasite Burden ◽  
Salivary Protein ◽  
Sand Fly ◽  
Human Neutrophils ◽  
Chemotactic Protein ◽  
The Impact

AbstractApart from bacterial formyl peptides or viral chemokine mimicry, a non-vertebrate or insect protein that directly attracts mammalian innate cells such as neutrophils has not been molecularly characterized. Here, we show that members of sand fly yellow salivary proteins induce in vitro chemotaxis of mouse, canine and human neutrophils in transwell migration or EZ-TAXIScan assays. We demonstrate murine neutrophil recruitment in vivo using flow cytometry and two-photon intravital microscopy in Lysozyme-M-eGFP transgenic mice. We establish that the structure of this ~ 45 kDa neutrophil chemotactic protein does not resemble that of known chemokines. This chemoattractant acts through a G-protein-coupled receptor and is dependent on calcium influx. Of significance, this chemoattractant protein enhances lesion pathology (P < 0.0001) and increases parasite burden (P < 0.001) in mice upon co-injection with Leishmania parasites, underlining the impact of the sand fly salivary yellow proteins on disease outcome. These findings show that some arthropod vector-derived factors, such as this chemotactic salivary protein, activate rather than inhibit the host innate immune response, and that pathogens take advantage of these inflammatory responses to establish in the host.

scholarly journals A Case of COVID-19-Related Thrombocytopenia and Leukopenia in an Adolescent with Mild Symptoms

Children ◽  
2021 ◽  
Vol 8 (6) ◽  
pp. 509
Author(s):  
Lydia Kossiva ◽  
Athanasios Thirios ◽  
Eleni Panagouli ◽  
Alexandros Panos ◽  
Stavroula Lampidi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Viral Infection ◽  
Nasal Congestion ◽  
Pediatric Population ◽  
Clinical Manifestations ◽  
Bone Marrow Aspiration ◽  
White Blood Count ◽  
Chronic Obstructive ◽  
First Case ◽  
The Impact

Since the beginning of the COVID-19 pandemic, there have been numerous reports and reviews on the complications caused by the disease, analyzing the acute and chronic consequences. The main symptoms of SARS-CoV-2 are dry cough, fever, and fatigue. COVID-19 appears to affect all systems, including renal, cardiovascular, circulatory, and respiratory systems, causing chronic obstructive pulmonary disease. We report on a 14-year-old male adolescent, who presented with thrombocytopenia (platelet count 92 × 109 /L) and leukopenia (white blood count 4.2 × 103 /μL) that was observed two months ago. Ten days before the first blood test, a viral infection with nasal congestion and runny nose was reported, without other accompanying symptoms. Viral antibodies screening revealed positivity for all the three specific COVID-19 antibodies. Further haematological evaluation with bone marrow aspiration revealed non-specific dysplastic features of the red cell and megakaryocyte progenitors. Although haematological alterations due to COVID-19 infection are available from adult patients’ reports, the effect of COVID-19 infection in the pediatric population is underestimated and this is the first case with such haematological involvement. Noteworthy, in the current case, the impact of the COVID-19 infection was not related to the severity of the disease, as the symptoms were mild. In similar cases, bone marrow aspiration would not be performed as a part of routine work-up. Thus, it is important when evaluating pediatric patients with COVID-19 infection to search and report those alterations in order to better understand the impact and the spectrum of clinical manifestations of the specific viral infection in children and adolescents.

scholarly journals Clinical Management of Hypertension, Inflammation and Thrombosis in Hospitalized COVID-19 Patients: Impact on Survival and Concerns

2021 ◽  
Vol 10 (5) ◽  
pp. 1073
Author(s):  
Patricia Martínez-Botía ◽  
Ángel Bernardo ◽  
Andrea Acebes-Huerta ◽  
Alberto Caro ◽  
Blanca Leoz ◽  
...  
Keyword(s):  
Arterial Hypertension ◽  
Clinical Management ◽  
Cox Regression ◽  
Angiotensin Receptor Blockers ◽  
Treatment Options ◽  
Clinical Manifestations ◽  
Specific Treatment ◽  
Hospitalized Patients ◽  
Thrombosis Prophylaxis ◽  
The Impact

The most severe clinical manifestations of the Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are due to an unbalanced immune response and a pro-thrombotic hemostatic disturbance, with arterial hypertension or diabetes as acknowledged risk factors. While waiting for a specific treatment, the clinical management of hospitalized patients is still a matter of debate, and the effectiveness of treatments to manage clinical manifestations and comorbidities has been questioned. In this study, we aim to assess the impact of the clinical management of arterial hypertension, inflammation and thrombosis on the survival of COVID-19 patients. The Spanish cohorts included in this observational retrospective study are from HM Hospitales (2035 patients) and from Hospital Universitario Central de Asturias (72 patients). Kaplan Meier survival curves, Cox regression and propensity score matching analyses were employed, considering demographic variables, comorbidities and treatment arms (when opportune) as covariates. The management of arterial hypertension with angiotensin-converting enzyme 2 (ACE2) inhibitors or angiotensin receptor blockers is not detrimental, as was initially reported, and neither was the use of non-steroidal anti-inflammatory drugs (NSAIDs). On the contrary, our analysis shows that the use on itself of corticosteroids is not beneficial. Importantly, the management of COVID-19 patients with low molecular weight heparin (LMWH) as an anticoagulant significantly improves the survival of hospitalized patients. These results delineate the current treatment options under debate, supporting the effectiveness of thrombosis prophylaxis on COVID-19 patients as a first-line treatment without the need for compromising the treatment of comorbidities, while suggesting cautiousness when administering corticosteroids.

scholarly journals Conditioning with Fludarabine-Busulfan versus Busulfan-Cyclophosphamide Is Associated with Lower aGVHD and Higher Survival but More Extensive and Long Standing Bone Marrow Damage

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Xin He ◽  
YongBin Ye ◽  
XiaoJun Xu ◽  
Jing Wang ◽  
YuXian Huang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Conditioning Regimen ◽  
Clinical Manifestations ◽  
Major Complication ◽  
Clinical Situation ◽  
Hematopoietic Stem ◽  
T Cell Infiltration ◽  
Bone Marrow Damage ◽  
The Impact

Acute graft-versus-host disease (aGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and a major cause of nonrelapse mortality after allo-HSCT. A conditioning regimen plays a pivotal role in the development of aGVHD. To provide a platform for studying aGVHD and evaluating the impact of different conditioning regimens, we established a murine aGVHD model that simulates the clinical situation and can be conditioned with Busulfan-Cyclophosphamide (Bu-Cy) and Fludarabine-Busulfan (Flu-Bu). In our study, BALB/c mice were conditioned with Bu-Cy or Flu-Bu and transplanted with 2×107 bone marrow cells and 2×107 splenocytes from either allogeneic (C57BL/6) or syngeneic (BALB/c) donors. The allogeneic recipients conditioned with Bu-Cy had shorter survivals (P<0.05), more severe clinical manifestations, and higher hepatic and intestinal pathology scores, associated with increased INF-γ expression and diminished IL-4 expression in serum, compared to allogeneic recipients conditioned with Flu-Bu. Moreover, higher donor-derived T-cell infiltration and severely impaired B-cell development were seen in the bone marrow of mice, exhibiting aGVHD and conditioned with Flu-Bu. Our study showed that the conditioning regimen with Bu-Cy resulted in more severe aGVHD while the Flu-Bu regimen was associated with more extensive and long standing bone marrow damage.

scholarly journals Numerical Studies of the Effects of Water Capsules on Self-Healing Efficiency and Mechanical Properties in Cementitious Materials

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Haoliang Huang ◽  
Guang Ye
Keyword(s):  
Mechanical Properties ◽  
Tensile Strength ◽  
Elastic Modulus ◽  
Cementitious Materials ◽  
Self Healing ◽  
Negative Effects ◽  
Numerical Studies ◽  
Healing Efficiency ◽  
The Impact ◽  
Positive Effect

In this research, self-healing due to further hydration of unhydrated cement particles is taken as an example for investigating the effects of capsules on the self-healing efficiency and mechanical properties of cementitious materials. The efficiency of supply of water by using capsules as a function of capsule dosages and sizes was determined numerically. By knowing the amount of water supplied via capsules, the efficiency of self-healing due to further hydration of unhydrated cement was quantified. In addition, the impact of capsules on mechanical properties was investigated numerically. The amount of released water increases with the dosage of capsules at different slops as the size of capsules varies. Concerning the best efficiency of self-healing, the optimizing size of capsules is 6.5 mm for capsule dosages of 3%, 5%, and 7%, respectively. Both elastic modulus and tensile strength of cementitious materials decrease with the increase of capsule. The decreasing tendency of tensile strength is larger than that of elastic modulus. However, it was found that the increase of positive effect (the capacity of inducing self-healing) of capsules is larger than that of negative effects (decreasing mechanical properties) when the dosage of capsules increases.

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