scholarly journals Comparison of whole blood and spleen transcriptional signatures over the course of an experimental malaria infection

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Carlos Talavera-López ◽  
Yaw Bediako ◽  
Jing-wen Lin ◽  
John Joseph Valletta ◽  
Mario Recker ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Responses ◽  
Whole Blood ◽  
Peripheral Blood ◽  
Lymphoid Organ ◽  
Splenic Tissue ◽  
Specific Gene ◽  
Learning Approaches ◽  
Transcriptome Data ◽  
Cellular Immune

Abstract Although the spleen is broadly accepted as the major lymphoid organ involved in generating immune responses to the erythrocytic stages of the malaria parasite, Plasmodium, human splenic tissue is not readily available in most cases. As a result, most studies of malaria in humans rely on peripheral blood to assess cellular immune responses to malaria. The suitability of peripheral blood as a proxy for splenic immune responses is however unknown. Here, we have simultaneously analysed the transcriptomes of whole blood and spleen over 12 days of erythrocytic stage Plasmodium chabaudi infection in C57BL/6 mice. Using both unsupervised and directed approaches, we compared gene expression between blood and spleen over the course of infection. Taking advantage of publicly available datasets, we used machine learning approaches to infer cell proportions and cell-specific gene expression signatures from our whole tissue transcriptome data. Our findings demonstrate that spleen and blood are quite dissimilar, sharing only a small amount of transcriptional information between them, with transcriptional differences in both cellular composition and transcriptional activity. These results suggest that while blood transcriptome data may be useful in defining surrogate markers of protection and pathology, they should not be used to predict specific immune responses occurring in lymphoid organs.

Abstract 3259: Leukocyte Subset Specific Gene Expression In Acute Stroke Patients

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Mateusz G Adamski ◽  
Yan Li ◽  
Hua Yu ◽  
Erin Wagner ◽  
Sareen Amarjeet ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Stroke ◽  
Whole Blood ◽  
Peripheral Blood ◽  
Fold Increase ◽  
Specific Gene ◽  
Related Gene ◽  
Stroke Patients ◽  
Leukocyte Subset ◽  
Control Subjects

Background: Alterations in gene expression in the peripheral blood of patients with acute stroke have been demonstrated using microarray technology. Whole blood and peripheral blood mononuclear cells (PBMCs) were used in prior studies in which panels of genes diagnostic for stroke were developed. We aimed to determine the cellular sources of alterations in gene expression by studying individual leukocyte subsets. Methods: The expression of four genes previously found to be upregulated in ischemic and hemorrhagic stroke (IL1R2, S100A9, ETS2 and F5) was measured in four leukocyte subsets: CD14+ monocytes, CD4+ T cell lymphocytes, CD20+ B cell lymphocytes and PBMCs. These four genes had been reported in at least two of the previously published stroke-related gene panels. Peripheral blood was obtained from six acute stroke patients (all <48 hours from symptom onset) and 6 age, race and sex matched control subjects. Leukocytes were separated from whole blood using density gradient centrifugation and column magnetic bead cell sorting. The purity of separated leukocyte subsets exceeded 90% and was verified with flow cytometry. Messenger RNA was isolated from each leukocyte subset and analyzed by two step RT PCR and qPCR. The expression of the four stroke-related genes was compared to the expression of a housekeeping gene (GAPDH). The relative expression of individual genes and of the 4 gene panel within cellular subsets was compared between stroke patients and control subjects. Results: Individually, IL1R2 and S100A9 were significantly over-expressed in stroke patients with a 10 fold increase for IL1R2 in PBMCs (p<0.05) and a 3 fold increase for S100A9 in the CD4+ T and CD20+ B lymphocyte subsets (p<0.05). When analyzed as a panel of four genes the expression of IL1R2, S100A9, ETS2 and F5 was significantly higher in both the CD4+ T lymphocytes (p<0.05) and CD20+ B lymphocytes (p<0.05) of stroke patients but not in the monocytes or the PBMCs. Conclusion: These results show the potential diagnostic value of selected genes from panels previously found in microarray studies in stroke patients. They also emphasize the value of panel analysis over that of single gene expression and the potential cellular specificity of alterations in gene expression. Analysis of whole blood and PBMCs alone may not reflect important dynamic changes in stroke-related gene expression.

Uninfected erythrocytes inhibit Plasmodium falciparum–induced cellular immune responses in whole-blood assays

Blood ◽  
2004 ◽  
Vol 103 (8) ◽  
pp. 3084-3092 ◽  
Author(s):  
Siske S. Struik ◽  
Fakhreldin M. Omer ◽  
Katerina Artavanis-Tsakonas ◽  
Eleanor M. Riley
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Whole Blood ◽  
Peripheral Blood ◽  
Blood Monocytes ◽  
Peripheral Blood Mononuclear ◽  
Antigen Uptake ◽  
Cellular Immune Responses ◽  
Cellular Immune

Abstract Whole-blood assays (WBAs) have been successfully used as a simple tool for immuno-epidemiological field studies evaluating cellular immune responses to mycobacterial and viral antigens. Rather unexpectedly, we found very poor cytokine responses to malaria antigens in WBAs in 2 immuno-epidemiological studies carried out in malaria endemic populations in Africa. We have therefore conducted a detailed comparison of cellular immune responses to live (intact) and lysed malaria-infected erythrocytes in WBAs and in peripheral blood mononuclear cell (PBMC) cultures. We observed profound inhibition of both proliferative and interferon-γ responses to malarial antigens in WBAs as compared with PBMC cultures. This inhibition was seen only for malaria antigens and could not be overcome by increasing either antigen concentration or responder cell numbers. Inhibition was mediated by intact erythrocytes and occurred early in the culture period, suggesting that failure of antigen uptake might underlie the lack of T-cell responses. In support of this hypothesis, we have shown that intact uninfected erythrocytes specifically inhibit phagocytosis of infected red blood cells by peripheral blood monocytes. We propose that specific biochemical interactions with uninfected erythrocytes inhibit the phagocytosis of malaria-infected erythrocytes and that this may impede T-cell recognition in vivo. (Blood. 2004; 103:3084-3092)

scholarly journals Distinct patterns of whole blood transcriptional responses are induced in mice following immunisation with adenoviral and poxviral vector vaccines encoding the same antigen

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Dylan Sheerin ◽  
Christina Dold ◽  
Daniel O’Connor ◽  
Andrew J. Pollard ◽  
Christine S. Rollier
Keyword(s):  
Gene Expression ◽  
Single Dose ◽  
Immune Responses ◽  
Whole Blood ◽  
Viral Vector ◽  
Production Costs ◽  
Specific Gene ◽  
Type I ◽  
Transcriptional Responses ◽  
Response Expression

Abstract Background Viral vectors, including adenovirus (Ad) and modified vaccinia Ankara (MVA), have gained increasing attention as vaccine platforms in recent years due to their capacity to express antigens from a wide array of pathogens, their rapid induction of humoral and cellular protective immune responses, and their relatively low production costs. In particular, the chimpanzee Ad vector, ChAdOx1, has taken centre stage as a leading COVID-19 vaccine candidate. However, despite mounting data, both clinical and pre-clinical, demonstrating effective induction of adaptive immune responses, the innate immune signals that precede the protective responses that make these vectors attractive vaccine platforms remain poorly understood. Results In this study, a mouse immunisation model was used to evaluate whole blood gene expression changes 24 h after either a single dose or heterologous prime-boost regimen of an Ad and/or MVA vaccine. We demonstrate through comparative analysis of Ad vectors encoding different antigens that a transgene product-specific gene signature can be discerned from the vector-induced transcriptional response. Expression of genes involved in TLR2 stimulation and γδ T cell and natural killer cell activation were induced after a single dose of Ad, while MVA led to greater expression of type I interferon genes. The order of prime-boost combinations was found to influence the magnitude of the gene expression changes, with MVA/Ad eliciting greater transcriptional perturbation than Ad/MVA. Contrasting the two regimens revealed significant enrichment of epigenetic regulation pathways and augmented expression of MHC class I and II molecules associated with MVA/Ad. Conclusion These data demonstrate that the order in which vaccines from heterologous prime-boost regimens are administered leads to distinct transcriptional responses and may shape the immune response induced by such combinations. The characterisation of early vaccine-induce responses strengthens our understanding of viral vector vaccine mechanisms of action ahead of their characterisation in human clinical trials and are a valuable resource to inform the pre-clinical design of appropriate vaccine constructs for emerging infectious diseases.

scholarly journals Dysregulation of MS risk genes and pathways at distinct stages of disease

2017 ◽  
Vol 4 (3) ◽  
pp. e337 ◽  
Author(s):  
Sundararajan Srinivasan ◽  
Marco Di Dario ◽  
Alessandra Russo ◽  
Ramesh Menon ◽  
Elena Brini ◽  
...  
Keyword(s):  
Gene Expression ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Gene List ◽  
Literature Mining ◽  
Specific Gene ◽  
Healthy Population ◽  
Gene Expressions ◽  
Altered Expression ◽  
Risk Genes

Objective:To perform systematic transcriptomic analysis of multiple sclerosis (MS) risk genes in peripheral blood mononuclear cells (PBMCs) of subjects with distinct MS stages and describe the pathways characterized by dysregulated gene expressions.Methods:We monitored gene expression levels in PBMCs from 3 independent cohorts for a total of 297 cases (including clinically isolated syndromes (CIS), relapsing-remitting MS, primary and secondary progressive MS) and 96 healthy controls by distinct microarray platforms and quantitative PCR. Differential expression and pathway analyses for distinct MS stages were defined and validated by literature mining.Results:Genes located in the vicinity of MS risk variants displayed altered expression in peripheral blood at distinct stages of MS compared with the healthy population. The frequency of dysregulation was significantly higher than expected in CIS and progressive forms of MS. Pathway analysis for each MS stage–specific gene list showed that dysregulated genes contributed to pathogenic processes with scientific evidence in MS.Conclusions:Systematic gene expression analysis in PBMCs highlighted selective dysregulation of MS susceptibility genes playing a role in novel and well-known pathogenic pathways.

scholarly journals Stereotyped and specific gene expression programs in human innate immune responses to bacteria

2002 ◽  
Vol 99 (2) ◽  
pp. 972-977 ◽  
Author(s):  
J. C. Boldrick ◽  
A. A. Alizadeh ◽  
M. Diehn ◽  
S. Dudoit ◽  
C. L. Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Responses ◽  
Innate Immune ◽  
Specific Gene ◽  
Innate Immune Responses ◽  
Specific Gene Expression
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