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

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.

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

Infection and Immunity ◽

10.1128/iai.00764-19 ◽

2019 ◽

Vol 88 (3) ◽

Cited By ~ 1

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.

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Early diagnosis using canonical discriminant analysis of innate immune receptor gene expression profiles in a murine infectious or sterile systemic inflammation model

Journal of Trauma and Acute Care Surgery ◽

10.1097/ta.0000000000001789 ◽

2018 ◽

Vol 84 (4) ◽

pp. 583-589

Author(s):

Goro Tajima ◽

Ayako Tokunaga ◽

Takahiro Umehara ◽

Kazuya Ikematsu ◽

Junya Miyamoto ◽

...

Keyword(s):

Gene Expression ◽

Discriminant Analysis ◽

Early Diagnosis ◽

Systemic Inflammation ◽

Expression Profiles ◽

Receptor Gene ◽

Gene Expression Profiles ◽

Canonical Discriminant Analysis ◽

Innate Immune ◽

Receptor Gene Expression

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Distinct Innate Immune Gene Expression Profiles in Non-Melanoma Skin Cancer of Immunocompetent and Immunosuppressed Patients

PLoS ONE ◽

10.1371/journal.pone.0040754 ◽

2012 ◽

Vol 7 (7) ◽

pp. e40754 ◽

Cited By ~ 13

Author(s):

Beda Muehleisen ◽

Shang Brian Jiang ◽

Julie A. Gladsjo ◽

Monika Gerber ◽

Tissa Hata ◽

...

Keyword(s):

Gene Expression ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Innate Immune ◽

Immune Gene ◽

Immune Gene Expression ◽

Non Melanoma Skin Cancer ◽

Immunosuppressed Patients ◽

Innate Immune Gene ◽

Melanoma Skin

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Early Activation of the Innate Immunity and Specific Cellular Immune Pathways after Vaccination with a Live Intranasal Viral Vaccine and Challenge with Bovine Parainfluenza Type 3 Virus

Vaccines ◽

10.3390/vaccines10010104 ◽

2022 ◽

Vol 10 (1) ◽

pp. 104

Author(s):

Piet Nuijten ◽

Natalie Cleton ◽

Jeroen van der Loop ◽

Birgit Makoschey ◽

Wilco Pulskens ◽

...

Keyword(s):

Gene Expression ◽

Immune Response ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Innate Immune ◽

Wild Type ◽

Immune Pathways ◽

Cellular Immune ◽

Type 3 ◽

Virus Strains

Bovine parainfluenza type 3 (BPIV3) and bovine respiratory syncytial virus (BRSV) may cause bovine respiratory disease (BRD) in very young calves, and therefore vaccination should induce protection at the youngest age and as quickly as possible. This can be achieved by intranasal vaccination with a vaccine containing live attenuated BRSV and BPIV3 virus strains. The objective of this study was to measure gene expression levels by means of RT-qPCR of proteins involved in the innate and adaptive immune response in the nasopharyngeal mucosae after administration of the above-mentioned vaccine and after challenge with BPIV3. Gene expression profiles were different between (i) vaccinated, (ii) nonvaccinated-challenged, and (iii) vaccinated-challenged animals. In nonvaccinated-challenged animals, expression of genes involved in development of disease symptoms and pathology were increased, however, this was not the case after vaccination. Moreover, gene expression patterns of vaccinated animals reflected induction of the antiviral and innate immune pathways as well as an initial Th1 (cytotoxic) cellular response. After challenge with BPIV3, the vaccinated animals were protected against nasal shedding of the challenge virus and clinical symptoms, and in parallel the expression levels of the investigated genes had returned to values that were found before vaccination. In conclusion, in comparison to the virulent wild-type field isolates, the two virus strains in the vaccine have lost their capacity to evade the immune response, resulting in the induction of an antiviral state followed by a very early activation of innate immune and antiviral responses as well as induction of specific cellular immune pathways, resulting in protection. The exact changes in the genomes of these vaccine strains leading to attenuation have not been identified. These data represent the real-life situation and can serve as a basis for further detailed research. This is the first report describing the effects on immune gene expression profiles in the nasal mucosae induced by intranasal vaccination with a bivalent, live BRSV-BPI3V vaccine formulation in comparison to wild-type infection with a virulent BPI3V strain.

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Tensor Decomposition of Stimulated Monocyte and Macrophage Gene Expression Profiles Identifies Neurodegenerative Disease-specific Trans-eQTLs

10.1101/499509 ◽

2018 ◽

Cited By ~ 1

Author(s):

Satesh Ramdhani ◽

Elisa Navarro ◽

Evan Udine ◽

Brian M. Schilder ◽

Madison Parks ◽

...

Keyword(s):

Gene Expression ◽

Genetic Variants ◽

Gene Networks ◽

Disease Risk ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Tensor Decomposition ◽

Innate Immune ◽

Primary Role ◽

Expression Of Genes

AbstractRecent human genetic studies suggest that cells of the innate immune system have a primary role in the pathogenesis of neurodegenerative diseases. However, the results from these studies often do not elucidate how the genetic variants affect the biology of these cells to modulate disease risk. Here, we applied a tensor decomposition method to uncover disease-associated gene networks linked to distal genetic variation in stimulated human monocytes and macrophages gene expression profiles. We report robust evidence that some disease-associated genetic variants affect the expression of multiple genes in trans. These include a Parkinson’s disease locus influencing the expression of genes mediated by a protease that controls lysosomal function, and Alzheimer’s disease loci influencing the expression of genes involved in type 1 interferon signaling, myeloid phagocytosis, and complement cascade pathways. Overall, we uncover gene networks in induced innate immune cells linked to disease-associated genetic variants, which may help elucidate the underlying biology of disease.

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