Changes in selected subpopulations of lymphocytes in dogs infected with Babesia canis treated with imidocarb

2015 ◽  
Vol 43 (02) ◽  
pp. 94-100 ◽  
Author(s):  
Ł. Jarosz ◽  
M. Kalinowski ◽  
M. Staniec ◽  
Z. Grądzki ◽  
B. Salmons ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Immune Cell ◽  
Clinical Signs ◽  
Babesia Canis ◽  
Healthy Control ◽  
Group 2 ◽  
Physiological Values ◽  
Cell Phenotypes ◽  
Lymphocyte Populations ◽  
Lymphocyte Fraction

SummaryObjective: The purpose of this study was to track changes in selected subpopulations of lymphocytes in the blood of dogs infected with Babesia (B.) canis and treated with imidocarb. Material and methods: The study included 16 dogs divided into two groups. The first group (n = 6) consisted of healthy control animals. Dogs of the second group (n = 10) were infected with B. canis and after establishment of the diagnosis each animal received a single dose of imidocarb (5 mg/kg). Flow cytometry was used to enumerate several immune cell phenotypes. Results: It was concluded that the invasion of B. canis contributes to the decreased percentage of CD3+, CD4+, CD8+, CD21+ lymphocytes in the blood of infected animals. The decreased level of tested subpopulations of lymphocytes in group 2 persisted for the entire 12-day period of the test. After the administration of imidocarb, each tested lymphocyte fraction in the blood of the dogs with babesiosis increased, but did not reach physiological values. Conclusion: The presented results indicate that the resolution of clinical signs associated with babesiosis may be related to the stimulation and intensity of cellular immunity, dependent on the CD4+ T cells profile. After administration of imidocarb, the parasitemia is cleared which allows the recovery of the lymphocyte populations.

scholarly journals Zoonotic vaccinia virus strains belonging to different genetic clades exhibit immunomodulation abilities that are proportional to their virulence

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Karine Lima Lourenço ◽  
Leandro Andrade Chinália ◽  
Lethícia Ribeiro Henriques ◽  
Rodrigo Araújo Lima Rodrigues ◽  
Flávio Guimarães da Fonseca
Keyword(s):  
Immune Responses ◽  
Vaccinia Virus ◽  
Murine Model ◽  
Immune Cell ◽  
Clinical Signs ◽  
Vaccinia Viruses ◽  
Biological Aspects ◽  
Group 2

Abstract Background The vaccinia virus (VACV) isolates, Guarani P1 virus (GP1V) and Passatempo virus (PSTV), were isolated during zoonotic outbreaks in Brazil. Each one of them belongs to two different VACV clades, defined by biological aspects that include virulence in mice and phylogenetic analysis. Considering that information about how vaccinia viruses from different groups elicit immune responses in animals is scarce, we investigated such responses in mice infected either by GP1V (group 2) or PSTV (group 1), using VACV Western Reserve strain (VACV-WR) as control. Methods The severity of the infections was evaluated in BALB/c mice considering diverse clinical signs and defined scores, and the immune responses triggered by GP1V and PSTV infections were analysed by immune cell phenotyping and intra-cytoplasmic cytokines detection. Results We detected a reduction in total lymphocytes (CD3 +), macrophages (CD14 +), and NK cells (CD3-CD49 +) in animals infected with VACV-WR or GP1V. The VACV-WR and GP1V viruses, belonging to the most virulent group in a murine model, were able to down-modulate the cell immune responses upon mice infection. In contrast, PSTV, a virus considered less virulent in a murine model, showed little ability to down-modulate the mice immune responses. Mice infected with VACV-WR and GP1V viruses presented significant weight loss and developed lesions in their spleens, as well as damage to liver and lungs whereas mice infected with PSTV developed only moderate clinical signs. Conclusions Our results suggest that VACV immunomodulation in vivo is clade-related and is proportional to the strain’s virulence upon infection. Our data corroborate the classification of the different Brazilian VACV isolates into clades 1 and 2, taking into account not only phylogenetic criteria, but also clinical and immunological data.

scholarly journals Zoonotic Vaccinia Viruses Belonging to Different Genetic Clades Exhibit Immunomodulation Abilities That Are Proportional to Their Pathogenic Potential

2021 ◽  
Author(s):  
Karine Lima Lourenço ◽  
Leandro Andrade Chinália ◽  
Lethícia Rodrigues Henriques ◽  
Rodrigo Araújo Lima Rodrigues ◽  
Flávio Guimarães da Fonseca
Keyword(s):  
Immune Responses ◽  
Immune Cell ◽  
Clinical Signs ◽  
Lung Damage ◽  
Pathogenic Potential ◽  
Cell Responses ◽  
Vaccinia Viruses ◽  
Group 2

Abstract BackgroundThe Vaccinia virus (VACV) isolates, Guarani P1 virus (GP1V) and Passatempo virus (PSTV), were isolated from zoonotic outbreaks in Brazil and belong to two different VACV clades, as defined by biological aspects that include virulence in mice and phylogenetic analysis. Considering that information about how vaccinia viruses from different groups elicit immune responses in animals is scarce, we investigated such responses in mice infected by GP1V (group 2) or PSTV (group 1) using VACV Western Reserve strain (WR) as control. MethodsThe severity of the infections was evaluated in BALB/c mice considering diverse clinical signs and defined scores, and the immune responses triggered by GP1V and PSTV infections were analysed by immune cell phenotyping and intra-cytoplasmic cytokines detection. ResultsInfected mice showed significant weight loss and developed spleen lesions as well as liver and lung damage. Mice infected with PSTV, however, developed only moderate clinical signs. We detected a reduction of total lymphocytes (CD3+), macrophages (CD14+) and NK cells (CD3-CD49+) in animals infected with VACV-WR or GP1V. VACV-WR was able to significantly downmodulate cell immune responses upon mice infection, and GP1V-infected animals also showed intense downmodulation in cell responses. Contrarily, PSTV presented little ability to downmodulate mice immune responses. ConclusionsOur results suggest that VACV immunomodulation in vivo is clade-related and is proportional to the strain virulence upon infection. Our data corroborate the classification of the different Brazilian VACV isolates in clades 1 and 2, taking into account not only phylogenetic criteria, but also clinical and immunological data.

scholarly journals A Rodent Model of Sulfur Mustard Hematologic Toxicity for the Efficacy Evaluation of Candidate Medical Countermeasures

2020 ◽  
Author(s):  
Phillip H Beske ◽  
Christina M Wilhelm ◽  
Jill A Harvilchuck ◽  
Gennady E Platoff Jr. ◽  
David T Yeung
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Immune Cell ◽  
Sulfur Mustard ◽  
Clinical Chemistry ◽  
Clinical Signs ◽  
Cell Populations ◽  
Hematologic Toxicity ◽  
Adult Rats ◽  
Medical Countermeasures

ABSTRACT Introduction While exposure to sulfur mustard (SM) is commonly associated with the production of vesicating dermal, ocular, and respiratory injuries, systemic damage to bone marrow and lymphatic tissue can decrease critical immune cell populations leading to higher susceptibility to life-threatening infection and septicemia. There are currently no approved medical countermeasures for SM-induced myelosuppression. An intravenous SM challenge model was developed in adult rats as a preliminary proof-of-principle platform to evaluate the efficacy of candidate immunostimulants. Materials and Methods Adult male and female Sprague Dawley rats were exposed to SM through tail vein injection. Toxicity progression was monitored through clinical observations, body weights, body temperatures, hematology, serum clinical chemistry, and flow cytometry of blood and bone marrow samples. Results Following SM exposure, overt toxicity progression was characterized by weight loss, changes in body temperature, and manifestation of toxic clinical signs (diarrhea, lethargy, hunched posture, rough hair coat, respiratory distress, and death). Drastic alterations in complete blood cell profiles included an early-onset lymphopenia followed by a delayed-onset neutropenia and thrombocytopenia. Only transient changes in serum clinical chemistry parameters were observed. Flow cytometry analysis of circulating blood revealed that B-cells were more predominantly affected by SM exposure than T-cells. Challenge with SM resulted in loss of hematopoietic and mesenchymal stem cell populations in the bone marrow. Conclusions The small animal model developed in this study replicates many key aspects of human SM exposures and should serve as a relevant, rapid, and cost-effective platform to screen candidate medical countermeasures for SM-induced hematologic toxicity.

scholarly journals Single-cell map of diverse immune phenotypes in the acute myeloid leukemia microenvironment

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Rongqun Guo ◽  
Mengdie Lü ◽  
Fujiao Cao ◽  
Guanghua Wu ◽  
Fengcai Gao ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Single Cell ◽  
Myeloid Leukemia ◽  
Immune Cell ◽  
Immune Surveillance ◽  
Cell Types ◽  
Developmental Trajectory ◽  
Significant Difference ◽  
Cell Phenotypes ◽  
Acute Myeloid

Abstract Background Knowledge of immune cell phenotypes, function, and developmental trajectory in acute myeloid leukemia (AML) microenvironment is essential for understanding mechanisms of evading immune surveillance and immunotherapy response of targeting special microenvironment components. Methods Using a single-cell RNA sequencing (scRNA-seq) dataset, we analyzed the immune cell phenotypes, function, and developmental trajectory of bone marrow (BM) samples from 16 AML patients and 4 healthy donors, but not AML blasts. Results We observed a significant difference between normal and AML BM immune cells. Here, we defined the diversity of dendritic cells (DC) and macrophages in different AML patients. We also identified several unique immune cell types including T helper cell 17 (TH17)-like intermediate population, cytotoxic CD4+ T subset, T cell: erythrocyte complexes, activated regulatory T cells (Treg), and CD8+ memory-like subset. Emerging AML cells remodels the BM immune microenvironment powerfully, leads to immunosuppression by accumulating exhausted/dysfunctional immune effectors, expending immune-activated types, and promoting the formation of suppressive subsets. Conclusion Our results provide a comprehensive AML BM immune cell census, which can help to select pinpoint targeted drug and predict efficacy of immunotherapy.

scholarly journals Shared associations identify causal relationships between gene expression and immune cell phenotypes

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Christiane Gasperi ◽  
Sung Chun ◽  
Shamil R. Sunyaev ◽  
Chris Cotsapas
Keyword(s):  
Complex Traits ◽  
Direct Evidence ◽  
Immune Cell ◽  
Genetic Locus ◽  
Causal Variant ◽  
Causal Relationships ◽  
Genetic Studies ◽  
Two Factors ◽  
Gene Regulatory ◽  
Cell Phenotypes

AbstractGenetic mapping studies have identified thousands of associations between common variants and hundreds of human traits. Translating these associations into mechanisms is complicated by two factors: they fall into gene regulatory regions; and they are rarely mapped to one causal variant. One way around these limitations is to find groups of traits that share associations, using this genetic link to infer a biological connection. Here, we assess how many trait associations in the same locus are due to the same genetic variant, and thus shared; and if these shared associations are due to causal relationships between traits. We find that only a subset of traits share associations, with many due to causal relationships rather than pleiotropy. We therefore suggest that simply observing overlapping associations at a genetic locus is insufficient to infer causality; direct evidence of shared associations is required to support mechanistic hypotheses in genetic studies of complex traits.

scholarly journals Alveolar compartmentalization of inflammatory and immune cell biomarkers in pneumonia-related ARDS

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Inès Bendib ◽  
Asma Beldi-Ferchiou ◽  
Frédéric Schlemmer ◽  
Mathieu Surenaud ◽  
Bernard Maitre ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Hospital Mortality ◽  
Distress Syndrome ◽  
Immune Cell ◽  
Routine Care ◽  
Clinical Endpoint ◽  
Blood Samples ◽  
Hla Dr ◽  
Serum Ratio ◽  
Immunocompetent Patients

Abstract Background Biomarkers of disease severity might help individualizing the management of patients with the acute respiratory distress syndrome (ARDS). Whether the alveolar compartmentalization of biomarkers has a clinical significance in patients with pneumonia-related ARDS is unknown. This study aimed at assessing the interrelation of ARDS/sepsis biomarkers in the alveolar and blood compartments and explored their association with clinical outcomes. Methods Immunocompetent patients with pneumonia-related ARDS admitted between 2014 and 2018 were included in a prospective monocentric study. Bronchoalveolar lavage (BAL) fluid and blood samples were obtained within 48 h of admission. Twenty-two biomarkers were quantified in BAL fluid and serum. HLA-DR+ monocytes and CD8+ PD-1+ lymphocytes were quantified using flow cytometry. The primary clinical endpoint of the study was hospital mortality. Patients undergoing a bronchoscopy as part of routine care were included as controls. Results Seventy ARDS patients were included. Hospital mortality was 21.4%. The BAL fluid-to-serum ratio of IL-8 was 20 times higher in ARDS patients than in controls (p < 0.0001). ARDS patients with shock had lower BAL fluid-to-serum ratio of IL-1Ra (p = 0.026), IL-6 (p = 0.002), IP-10/CXCL10 (p = 0.024) and IL-10 (p = 0.023) than others. The BAL fluid-to-serum ratio of IL-1Ra was more elevated in hospital survivors than decedents (p = 0.006), even after adjusting for SOFA and driving pressure (p = 0.036). There was no significant association between alveolar or alveolar/blood monocytic HLA-DR or CD8+ lymphocytes PD-1 expression and hospital mortality. Conclusions IL-8 was the most compartmentalized cytokine and lower BAL fluid-to-serum concentration ratios of IL-1Ra were associated with hospital mortality in patients with pneumonia-associated ARDS.

scholarly journals Combination-Feeding Causes Differences in Aspects of Systemic and Mucosal Immune Cell Phenotypes and Functions Compared to Exclusive Sow-Rearing or Formula-Feeding in Piglets

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1097
Author(s):  
Emily C. Radlowski ◽  
Mei Wang ◽  
Marcia H. Monaco ◽  
Sarah S. Comstock ◽  
Sharon M. Donovan
Keyword(s):  
Immune Cell ◽  
Arginase Activity ◽  
T Helper ◽  
Mesenteric Lymph Nodes ◽  
Immune Development ◽  
Mesenteric Lymph ◽  
Tnf Α ◽  
Activation Pathways ◽  
Cell Phenotypes ◽  
Oxide Synthase

Combination feeding (human milk and formula) is common and influences immune development compared to exclusive breastfeeding. Infant formulas contain prebiotics, which influence immune development. Herein, immune development of combination-fed (CF), sow-reared (SR) and formula-fed (FF) piglets, and the effect of prebiotics was tested. Piglets (n = 47) were randomized to: SR, FF, CF, FF+prebiotic (FP), and CF+prebiotic (CP). FP and CP received formula with galactooligosaccharides and inulin (4 g/L in a 4:1 ratio). CF and CP piglets were sow-reared for until d5 and then rotated between a sow and formula every 12 h. On day 21, piglets received an intraperitoneal injection of lipopolysaccharide 2 h prior to necropsy. Immune cells from blood, mesenteric lymph nodes (MLN), and spleen were phenotyped. Classical (nitric oxide synthase) and alternative (arginase activity) activation pathways were measured in isolated macrophages. Serum IL-6 and TNF-α were measured by ELISA. SR piglets had lower (p < 0.0001) CD4+ T-helper cells and higher (p < 0.0001) B-cells in PBMC than all other groups. CP piglets had higher (p < 0.0001) arginase activity compared to all other groups. FF piglets had higher (p < 0.05) IL-6 compared to both CF and SR, but were similar to FP and CP. Thus, CF, with or without prebiotics, differentially affected immunity compared to exclusively fed groups.

scholarly journals Sex- and age‐dependent alterations of splenic immune cell profile and NK cell phenotypes and function in C57BL/6J mice

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Kelly B. Menees ◽  
Rachael H. Earls ◽  
Jaegwon Chung ◽  
Janna Jernigan ◽  
Nikolay M. Filipov ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Sex Differences ◽  
Nk Cells ◽  
Immune Cell ◽  
Nk Cell ◽  
Spleen Weight ◽  
Age Related ◽  
And Function ◽  
Cell Phenotypes

Abstract Background Physiological homeostasis decline, immunosenescence, and increased risk for multiple diseases, including neurodegeneration, are all hallmarks of ageing. Importantly, it is known that the ageing process is sex-biased. For example, there are sex differences in predisposition for multiple age-related diseases, including neurodegenerative and autoimmune diseases. However, sex differences in age-associated immune phenotypes are not clearly understood. Results Here, we examined the effects of age on immune cell phenotypes in both sexes of C57BL/6J mice with a particular focus on NK cells. We found female-specific spleen weight increases with age and concordant reduction in the number of splenocytes per gram of spleen weight compared to young females. To evaluate sex- and age-associated changes in splenic immune cell composition, we performed flow cytometry analysis. In male mice, we observed an age-associated reduction in the frequencies of monocytes and NK cells; female mice displayed a reduction in B cells, NK cells, and CD8 + T cells and increased frequency of monocytes and neutrophils with age. We then performed a whole blood stimulation assay and multiplex analyses of plasma cytokines and observed age- and sex-specific differences in immune cell reactivity and basal circulating cytokine concentrations. As we have previously illustrated a potential role of NK cells in Parkinson’s disease, an age-related neurodegenerative disease, we further analyzed age-associated changes in NK cell phenotypes and function. There were distinct differences between the sexes in age-associated changes in the expression of NK cell receptors, IFN-γ production, and impairment of α-synuclein endocytosis. Conclusions This study demonstrates sex- and age-specific alterations in splenic lymphocyte composition, circulating cytokine/chemokine profiles, and NK cell phenotype and effector functions. Our data provide evidence that age-related physiological perturbations differ between the sexes which may help elucidate sex differences in age-related diseases, including neurodegenerative diseases, particularly Parkinson’s disease, where immune dysfunction is implicated in their etiology.

scholarly journals IMMU-68. SINGLE-CELL PROTEOMIC ANALYSIS OF IMMUNE CELL RESPONSE TO CHECKPOINT BLOCKADE USING 30-PARAMETER FLOW CYTOMETRY

2018 ◽  
Vol 20 (suppl_6) ◽  
pp. vi137-vi137
Author(s):  
Amber Giles ◽  
Leonard Nettey ◽  
Thomas Liechti ◽  
Margaret Beddall ◽  
Elizabeth Vera ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Single Cell ◽  
Cell Response ◽  
Proteomic Analysis ◽  
Immune Cell ◽  
Checkpoint Blockade ◽  
Immune Cell Response
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