scholarly journals Attenuated Rabies Virus Activates, while Pathogenic Rabies Virus Evades, the Host Innate Immune Responses in the Central Nervous System

2005 ◽  
Vol 79 (19) ◽  
pp. 12554-12565 ◽  
Author(s):  
Zhi W. Wang ◽  
Luciana Sarmento ◽  
Yuhuan Wang ◽  
Xia-qing Li ◽  
Vikas Dhingra ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Rabies Virus ◽  
Inflammatory Responses ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Innate Immune ◽  
Host Responses ◽  
Oligoadenylate Synthetase ◽  
Antiviral Responses ◽  
Inflammatory Chemokines

ABSTRACT Rabies virus (RV) induces encephalomyelitis in humans and animals. However, the pathogenic mechanism of rabies is not fully understood. To investigate the host responses to RV infection, we examined and compared the pathology, particularly the inflammatory responses, and the gene expression profiles in the brains of mice infected with wild-type (wt) virus silver-haired bat RV (SHBRV) or laboratory-adapted virus B2C, using a mouse genomic array (Affymetrix). Extensive inflammatory responses were observed in animals infected with the attenuated RV, but little or no inflammatory responses were found in mice infected with wt RV. Furthermore, attenuated RV induced the expression of the genes involved in the innate immune and antiviral responses, especially those related to the alpha/beta interferon (IFN-α/β) signaling pathways and inflammatory chemokines. For the IFN-α/β signaling pathways, many of the interferon regulatory genes, such as the signal transduction activation transducers and interferon regulatory factors, as well as the effector genes, for example, 2′-5′-oligoadenylate synthetase and myxovirus proteins, are highly induced in mice infected with attenuated RV. However, many of these genes were not up-regulated in mice infected with wt SHBRV. The data obtained by microarray analysis were confirmed by real-time PCR. Together, these data suggest that attenuated RV activates, while pathogenic RV evades, the host innate immune and antiviral responses.

scholarly journals Age-related differences in monocyte DNA methylation and immune function in healthy Kenyan adults and children

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Katherine R. Dobbs ◽  
Paula Embury ◽  
Emmily Koech ◽  
Sidney Ogolla ◽  
Stephen Munga ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Young Adults ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Innate Immune ◽  
Inflammatory Gene Expression ◽  
Cpg Sites ◽  
Age Related ◽  
Adults And Children

Abstract Background Age-related changes in adaptive and innate immune cells have been associated with a decline in effective immunity and chronic, low-grade inflammation. Epigenetic, transcriptional, and functional changes in monocytes occur with aging, though most studies to date have focused on differences between young adults and the elderly in populations with European ancestry; few data exist regarding changes that occur in circulating monocytes during the first few decades of life or in African populations. We analyzed DNA methylation profiles, cytokine production, and inflammatory gene expression profiles in monocytes from young adults and children from western Kenya. Results We identified several hypo- and hyper-methylated CpG sites in monocytes from Kenyan young adults vs. children that replicated findings in the current literature of differential DNA methylation in monocytes from elderly persons vs. young adults across diverse populations. Differentially methylated CpG sites were also noted in gene regions important to inflammation and innate immune responses. Monocytes from Kenyan young adults vs. children displayed increased production of IL-8, IL-10, and IL-12p70 in response to TLR4 and TLR2/1 stimulation as well as distinct inflammatory gene expression profiles. Conclusions These findings complement previous reports of age-related methylation changes in isolated monocytes and provide novel insights into the role of age-associated changes in innate immune functions.

scholarly journals n-3 Fatty acids, inflammation and immunity: new mechanisms to explain old actions

2013 ◽  
Vol 72 (3) ◽  
pp. 326-336 ◽  
Author(s):  
Philip C. Calder
Keyword(s):  
Fatty Acids ◽  
Inflammatory Responses ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Mechanisms Of Action ◽  
Lipid Mediators ◽  
Functional Responses ◽  
New Family ◽  
Epa And Dha ◽  
Novel Interactions

Numerous effects of n-3 fatty acids EPA and DHA on functional responses of cells involved in inflammation and immunity have been described. Fatty acid-induced modifications in membrane order and in the availability of substrates for eicosanoid synthesis are long-standing mechanisms that are considered important in explaining the effects observed. More recently, effects on signal transduction pathways and on gene expression profiles have been identified. Over the last 10 years or so, significant advances in understanding the mechanisms of action of n-3 fatty acids have been made. These include the identification of new actions of lipid mediators that were already described and of novel interactions among those mediators and the description of an entirely new family of lipid mediators, resolvins and protectins that have anti-inflammatory actions and are critical to the resolution of inflammation. It is also recognised that EPA and DHA can inhibit activation of the prototypical inflammatory transcription factor NF-κB. Recent studies suggest three alternative mechanisms by which n-3 fatty acids might have this effect. Within T-cells, as well as other cells of relevance to immune and inflammatory responses, EPA and DHA act to disrupt very early events involving formation of the structures termed lipid rafts which bring together various proteins to form an effective signalling platform. In summary, recent research has identified a number of new mechanisms of action that help to explain previously identified effects of n-3 fatty acids on inflammation and immunity.

Whole blood genome-wide gene expression profile in males after prolonged wakefulness and sleep recovery

2012 ◽  
Vol 44 (21) ◽  
pp. 1003-1012 ◽  
Author(s):  
R. Pellegrino ◽  
D. Y. Sunaga ◽  
C. Guindalini ◽  
R. C. S. Martins ◽  
D. R. Mazzotti ◽  
...  
Keyword(s):  
Gene Expression ◽  
Whole Blood ◽  
Inflammatory Responses ◽  
Expression Profiles ◽  
Killer Cell ◽  
Gene Expression Profiles ◽  
Sleep Loss ◽  
The Body ◽  
Dna Damage And Repair ◽  
Peripheral Tissues

Although the specific functions of sleep have not been completely elucidated, the literature has suggested that sleep is essential for proper homeostasis. Sleep loss is associated with changes in behavioral, neurochemical, cellular, and metabolic function as well as impaired immune response. Using high-resolution microarrays we evaluated the gene expression profiles of healthy male volunteers who underwent 60 h of prolonged wakefulness (PW) followed by 12 h of sleep recovery (SR). Peripheral whole blood was collected at 8 am in the morning before the initiation of PW (Baseline), after the second night of PW, and one night after SR. We identified over 500 genes that were differentially expressed. Notably, these genes were related to DNA damage and repair and stress response, as well as diverse immune system responses, such as natural killer pathways including killer cell lectin-like receptors family, as well as granzymes and T-cell receptors, which play important roles in host defense. These results support the idea that sleep loss can lead to alterations in molecular processes that result in perturbation of cellular immunity, induction of inflammatory responses, and homeostatic imbalance. Moreover, expression of multiple genes was downregulated following PW and upregulated after SR compared with PW, suggesting an attempt of the body to re-establish internal homeostasis. In silico validation of alterations in the expression of CETN3, DNAJC, and CEACAM genes confirmed previous findings related to the molecular effects of sleep deprivation. Thus, the present findings confirm that the effects of sleep loss are not restricted to the brain and can occur intensely in peripheral tissues.

scholarly journals Hemophilia A Inhibitor Subjects Show Unique PBMC Gene Expression Profiles That Include Up-Regulated Innate Immune Modulators

2020 ◽  
Vol 11 ◽  
Author(s):  
Ahmad Faisal Karim ◽  
Anthony R. Soltis ◽  
Gauthaman Sukumar ◽  
Christoph Königs ◽  
Nadia P. Ewing ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hemophilia A ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Innate Immune ◽  
Immune Modulators

scholarly journals Profiles of Local and Systemic Inflammation in the Outcome of Treatment of Human Cutaneous Leishmaniasis Caused by Leishmania (Viannia)

2019 ◽  
Vol 88 (3) ◽  
Author(s):  
Adriana Navas ◽  
Olga Fernández ◽  
Carolina Gallego-Marín ◽  
María del Mar Castro ◽  
Mariana Rosales-Chilama ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Responses ◽  
Treatment Failure ◽  
Cutaneous Leishmaniasis ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Neutrophil Activation ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Biopsy Specimens

ABSTRACT The immune mechanisms that contribute to the efficacy of treatment of cutaneous leishmaniasis (CL) are not fully understood. The aim of this study was to define immune correlates of the outcome of treatment of CL caused by Leishmania (Viannia) species during standard of care treatment with pentavalent antimonials. We conducted a comparative expression profiling of immune response genes in peripheral blood mononuclear cells (PBMCs) and lesion biopsy specimens obtained from CL patients before and at the end of treatment (EoT) with meglumine antimoniate. The ex vivo response of PBMCs to L. (V.) panamensis partially reflected that of lesion microenvironments. Significant downregulation of gene expression profiles consistent with local innate immune responses (monocyte and neutrophil activation and chemoattractant molecules) was observed at EoT in biopsy specimens of patients who cured (n = 8), compared to those from patients with treatment failure (n = 8). Among differentially expressed genes, pretreatment expression of CCL2 was significantly predictive of the therapeutic response (receiver operating characteristic [ROC] curve, area under the curve [AUC] = 0.82, P = 0.02). Polymorphisms in regulatory regions of the CCL2 promoter were analyzed in a pilot cohort of DNA samples from CL patients (cures, n = 20, and treatment failure, n = 20), showing putative association of polymorphisms rs13900(C/T) and rs2857656(G/C) with treatment outcome. Our data indicate that dampening gene expression profiles of monocyte and neutrophil activation characterize clinical cure after treatment of CL, supporting participation of parasite-sustained inflammation or deregulated innate immune responses in treatment failure.

scholarly journals Vitamin D-regulated Gene Expression Profiles: Species-specificity and Cell-specific Effects on Metabolism and Immunity

Endocrinology ◽  
2020 ◽  
Vol 162 (2) ◽  
Author(s):  
Vassil Dimitrov ◽  
Camille Barbier ◽  
Aiten Ismailova ◽  
Yifei Wang ◽  
Katy Dmowski ◽  
...  
Keyword(s):  
Vitamin D ◽  
Large Scale ◽  
Expression Profiles ◽  
Mammalian Target Of Rapamycin ◽  
Gene Expression Profiles ◽  
Innate Immune ◽  
Monocytic Cells ◽  
Specific Regulation ◽  
Regulated Gene Expression ◽  
Vitamin D Signaling

Abstract Vitamin D has pleiotropic physiological actions including immune system regulation, in addition to its classical role in calcium homeostasis. Hormonal 1,25-dihydroxyvitamin D (1,25D) signals through the nuclear vitamin D receptor, and large-scale expression profiling has provided numerous insights into its diverse physiological roles. To obtain a comprehensive picture of vitamin D signaling, we analyzed raw data from 94 (80 human, 14 mouse) expression profiles of genes regulated by 1,25D or its analogs. This identified several thousand distinct genes directly or indirectly up- or downregulated in a highly cell-specific manner in human cells using a 1.5-fold cut-off. There was significant overlap of biological processes regulated in human and mouse but minimal intersection between genes regulated in each species. Disease ontology clustering confirmed roles for 1,25D in immune homeostasis in several human cell types, and analysis of canonical pathways revealed novel and cell-specific roles of vitamin D in innate immunity. This included cell-specific regulation of several components of Nucleotide-binding Oligomerization Domain-like (NOD-like) pattern recognition receptor signaling, and metabolic events controlling innate immune responses. Notably, 1,25D selectively enhanced catabolism of branched-chain amino acids (BCAAs) in monocytic cells. BCAA levels regulate the major metabolic kinase mammalian Target of Rapamycin (mTOR), and pretreatment with 1,25D suppressed BCAA-dependent activation of mTOR signaling. Furthermore, ablation of BCAT1 expression in monocytic cells blocked 1,25D-induced increases in autophagy marker LAMP1. In conclusion, the data generated represents a powerful tool to further understand the diverse physiological roles of vitamin D signaling and provides multiple insights into mechanisms of innate immune regulation by 1,25D.

Gene expression profiles predict the possible regulatory role of OPN-mediated signaling pathways in rat liver regeneration

Gene ◽  
2016 ◽  
Vol 576 (2) ◽  
pp. 782-790 ◽  
Author(s):  
Gaiping Wang ◽  
Shasha Chen ◽  
Congcong Zhao ◽  
Xiaofang Li ◽  
Ling Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Liver Regeneration ◽  
Signaling Pathways ◽  
Rat Liver ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Regulatory Role ◽  
Rat Liver Regeneration

scholarly journals Dact gene expression profiles suggest a role for this gene family in integrating Wnt and TGF-β signaling pathways during chicken limb development

2013 ◽  
Vol 243 (3) ◽  
pp. 428-439 ◽  
Author(s):  
Lucimara Aparecida Sensiate ◽  
Débora R. Sobreira ◽  
Fernanda Cristina Da Veiga ◽  
Denner Jefferson Peterlini ◽  
Angelica Vasconcelos Pedrosa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Family ◽  
Signaling Pathways ◽  
Limb Development ◽  
Expression Profiles ◽  
Gene Expression Profiles

Distinct gene expression profiles provoked by polyacrylamide beads (Biogel) during chronic and acute inflammation in mice selected for maximal and minimal inflammatory responses

2016 ◽  
Vol 65 (4) ◽  
pp. 313-323 ◽  
Author(s):  
Jussara Gonçalves Fernandes ◽  
Tatiane Canhamero ◽  
Andrea Borrego ◽  
José Ricardo Jensen ◽  
Wafa Hanna Cabrera ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Inflammation ◽  
Inflammatory Responses ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Distinct Gene

scholarly journals Logic-based Analysis of Gene Expression Data Predicts Pathway Crosstalk between TNF, TGFB1 and EGF in Basal-like Breast Cancer

2019 ◽  
Author(s):  
Kyuri Jo ◽  
Beatriz Santos Buitrago ◽  
Minsu Kim ◽  
Sungmin Rhee ◽  
Carolyn Talcott ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Signaling Pathways ◽  
Expression Profiles ◽  
Formal System ◽  
Gene Expression Profiles ◽  
Breast Cancer Subtypes ◽  
Post Translational Modifications ◽  
Cancer Subtypes ◽  
Pathway Crosstalk

AbstractFor breast cancer, clinically important subtypes are well characterised at the molecular level in terms of gene expression profiles. In addition, signaling pathways in breast cancer have been extensively studied as therapeutic targets due to their roles in tumor growth and metastasis. However, it is challenging to put signaling pathways and gene expression profiles together to characterise biological mechanisms of breast cancer subtypes since many signaling events result from post-translational modifications, rather than gene expression differences.We present a logic-based approach to explain the differences in gene expression profiles among breast cancer subtypes using Pathway Logic and transcriptional network information. Pathway Logic is a rewriting-logic-based formal system for modeling biological pathways including post-translational modifications. Proposed method demonstrated its utility by constructing subtype-specific path from key receptors (TNFR, TGFBR1 and EGFR) to key transcription factor (TF) regulators (RELA, ATF2, SMAD3 and ELK1) and identifying potential pathway crosstalk via TFs in basal-specific paths, which could provide a novel insight on aggressive breast cancer subtypes.AvailabilityAnalysis result is available at http://epigenomics.snu.ac.kr/PL/

Sign in / Sign up

Export Citation Format

Share Document