scholarly journals 63 DNA methylome wide profile associates differentially methylated loci and regions with cow’s ileal lymph node response to Mycobacterium avium subsp. paratuberculosis

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 39-40
Author(s):  
Eveline M Ibeagha-Awemu ◽  
Suraj Bhattarai ◽  
Pier-Luc Dedemaine ◽  
Mengqi Wang ◽  
Stephanie D McKay ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Lymph Node ◽  
Immune Responses ◽  
Signaling Pathway ◽  
Cell Receptor ◽  
Negative Regulation ◽  
Term Survival ◽  
Host Immune Responses ◽  
Mycobacterium Avium Subsp Paratuberculosis

Abstract Johne’s Disease (JD), caused by Mycobacterium avim spp paratuberculosis (MAP), is a chronic and incurable disease of ruminants with devastating consequences to the dairy industry. MAP can alter the expression of genes and biological processes during the progression of JD. While some studies have examined the role of gene expression regulators like microRNA in the pathogenesis of JD, no study has explored the role of DNA methylation. This study therefore examined the effect of MAP on DNA methylation profile in the ileum lymph node (ILLN) of cows with subclinical MAP infection. DNA from ILLN tissues from five cows positive for MAP (MAP positive) and five negative cows (MAP negative) were extracted and subjected to whole genome bisulfite sequencing and bioinformatics analysis. A total of 6,394 differentially methylated cytosines (DMCs) and 3,946 differentially methylated regions (DMRs) (FDR < 0.05) were identified between MAP positive and negative cows. DMRs were annotated to 2,488 genes, including the promoters of 238 genes. Some genes with hypermethylated promoters like GRB10, EIF4E, SLC30A3, SOX30 or hypomethylated promoters like SLC11A1, HOXA4, SLC18A1 have been associated with JD or mycobacterial infections in cattle and/or humans. Functional annotation of DMR genes indicated enrichment in pathways previously associated with JD or human diseases with similar pathological conditions as JD, such as T/B cell receptor signaling pathway, Th17 cell differentiation, Cell adhesion molecules, Leukocyte transendothelial migration, HIF-1 signaling pathway and Chagas disease. Furthermore, enriched gene ontology terms like negative regulation of immune system process, negative regulation of cytokine secretion/production and negative regulation of inflammatory response suggest that MAP prevented or reduced the host immune response. Our data demonstrate that DNA methylation changes contribute to regulation of host immune responses to MAP infection and may be one of the mechanisms that MAP uses to subvert host immune responses for its long-term survival.

scholarly journals The DBL-1/TGF-β signaling pathway regulates pathogen-specific innate immune responses in C. elegans

2021 ◽  
Author(s):  
Bhoomi Madhu ◽  
Tina L. Gumienny
Keyword(s):  
Innate Immunity ◽  
Immune Responses ◽  
Signaling Pathway ◽  
Defense Responses ◽  
C Elegans ◽  
Host Immune Responses ◽  
Wide Range ◽  
Independent Functions ◽  
Multiple Cell

Innate immunity in animals is orchestrated by multiple cell signaling pathways, including the TGF-β; superfamily pathway. While the role of TGF-β signaling in innate immunity has been clearly identified, the requirement for this pathway in generating specific, robust responses to different bacterial challenges has not been characterized. Here, we address the role of DBL-1/TGF-β in regulating signature host defense responses to a wide range of bacteria in C. elegans. This work reveals a role of DBL-1/TGF-β in animal survival, organismal behaviors, and molecular responses in different environments. Additionally, we identify a novel role for SMA-4/Smad that suggests both DBL-1/TGF-β-dependent and -independent functions in host avoidance responses. RNA-seq analyses and immunity reporter studies indicate DBL-1/TGF-β differentially regulates target gene expression upon exposure to different bacteria. Furthermore, the DBL-1/TGF-β pathway is itself differentially affected by the bacteria exposure. Collectively, these findings demonstrate bacteria-specific host immune responses regulated by the DBL-1/TGF-β signaling pathway.

scholarly journals Whole Genome Methylation Analysis Reveals Role of DNA Methylation in Cow’s Ileal and Ileal Lymph Node Responses to Mycobacterium avium subsp. paratuberculosis Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Eveline M. Ibeagha-Awemu ◽  
Nathalie Bissonnette ◽  
Suraj Bhattarai ◽  
Mengqi Wang ◽  
Pier-Luc Dudemaine ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Immune Response ◽  
Lymph Node ◽  
Whole Genome ◽  
Metabolic Processes ◽  
Cellular Processes ◽  
Gut Immunity ◽  
Mycobacterium Avium Subsp Paratuberculosis ◽  
Go Terms

Johne’s Disease (JD), caused by Mycobacterium avium subsp paratuberculosis (MAP), is an incurable disease of ruminants and other animal species and is characterized by an imbalance of gut immunity. The role of MAP infection on the epigenetic modeling of gut immunity during the progression of JD is still unknown. This study investigated the DNA methylation patterns in ileal (IL) and ileal lymph node (ILLN) tissues from cows diagnosed with persistent subclinical MAP infection over a one to 4 years period. DNA samples from IL and ILLN tissues from cows negative (MAPneg) (n = 3) or positive for MAP infection (MAPinf) (n = 4) were subjected to whole genome bisulfite sequencing. A total of 11,263 and 62,459 differentially methylated cytosines (DMCs), and 1259 and 8086 differentially methylated regions (DMRs) (FDR<0.1) were found between MAPinf and MAPneg IL and ILLN tissues, respectively. The DMRs were found on 394 genes (denoted DMR genes) in the IL and on 1305 genes in the ILLN. DMR genes with hypermethylated promoters/5′UTR [3 (IL) and 88 (ILLN)] or hypomethylated promoters/5′UTR [10 (IL) and 25 (ILLN)] and having multiple functions including response to stimulus/immune response (BLK, BTC, CCL21, AVPR1A, CHRNG, GABRA4, TDGF1), cellular processes (H2AC20, TEX101, GLA, NCKAP5L, RBM27, SLC18A1, H2AC20BARHL2, NLGN3, SUV39H1, GABRA4, PPA1, UBE2D2) and metabolic processes (GSTO2, H2AC20, SUV39H1, PPA1, UBE2D2) are potential DNA methylation candidate genes of MAP infection. The ILLN DMR genes were enriched for more biological process (BP) gene ontology (GO) terms (n = 374), most of which were related to cellular processes (27.6%), biological regulation (16.6%), metabolic processes (15.4%) and response to stimulus/immune response (8.2%) compared to 75 BP GO terms (related to cellular processes, metabolic processes and transport, and system development) enriched for IL DMR genes. ILLN DMR genes were enriched for more pathways (n = 47) including 13 disease pathways compared with 36 enriched pathways, including 7 disease/immune pathways for IL DMR genes. In conclusion, the results show tissue specific responses to MAP infection with more epigenetic changes (DMCs and DMRs) in the ILLN than in the IL tissue, suggesting that the ILLN and immune processes were more responsive to regulation by methylation of DNA relative to IL tissue. Our data is the first to demonstrate a potential role for DNA methylation in the pathogenesis of MAP infection in dairy cattle.

scholarly journals PSVIII-15 Genome wide DNA methylation analysis reveals role of DNA methylation in cow’s ileal response to Mycobacterium avium subsp. paratuberculosis

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 260-261
Author(s):  
Eveline M Ibeagha-Awemu ◽  
Suraj Bhattarai ◽  
Pier-Luc Dedemaine ◽  
Mengqi Wang ◽  
Stephanie D McKay ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Mycobacterium Avium ◽  
Molecular Mechanisms ◽  
Elisa Test ◽  
Mycobacterium Avium Subsp ◽  
Host Immune Responses ◽  
Intergenic Regions ◽  
Mycobacterium Avium Subsp Paratuberculosis ◽  
The Impact

Abstract Several investigations on disease progression of Mycobacterium avium subsp. paratuberculosis (MAP) infection in dairy cows have revealed molecular mechanisms including genes and pathways implicated in MAP pathogenesis. Epigenetic processes including DNA methylation are known to regulate the expression of genes and many biological processes. However, limited studies have examined the role of DNA methylation in the pathogenesis of Johne’s disease (JD). This study examined the impact of subclinical MAP infection on DNA methylation profile in the ileum of cows, the site of initial interaction between MAP and host. DNA from ileum tissues from five cows positive for MAP (direct fecal qPCR and blood ELISA test; MAP+/+) and 5 cows negative for MAP (MAP-/-) were subjected to whole genome bisulfite sequencing and bioinformatics analysis. 2000 differentially methylated cytosines (DMCs; FDR< 0.05) and 205 differentially methylated regions (DMRs; P < 0.01) were detected. Majority of DMCs and DMRs are located in intergenic regions (87.2% and 57.1%) followed by intronic regions (12.8% and 30.7%) of genes, respectively. Some DMCs are located on 250 genes including genes that were previously identified to be associated with JD (e.g. IL-12RB2, CD38). Interestingly, CD38, known to play roles in the effective containment of mycobacteria within granulomata in cows and genetic polymorphisms in IL-12RB2 are associated with JD and human Crohn’s disease. Also, several genes of the solute carrier family including SLC13A3, SLC15A1, SLC17A7, SLC25A21, SLC25A38 and SLC9A9 harbored DMCs. Some members of this gene family participate in pathogen clearance and have associations with JD. Our data suggest that DNA methylation changes may have regulatory roles in host (ileum) response to MAP infection. Our data therefore suggest that DNA methylation changes contribute to the regulation of host response to MAP pathogenesis and may be one of the mechanisms that MAP uses to subvert host immune responses for its survival.

Role of convalescent plasma therapy in new Coronavirus disease (nCOVID-19): A review

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 546-549
Author(s):  
Shweta Dadarao Parwe ◽  
Milind Abhimanyu Nisargandha ◽  
Rishikesh Thakre
Keyword(s):  
Clinical Trial ◽  
Immune Responses ◽  
Indian Population ◽  
Preventive Treatment ◽  
The Body ◽  
Therapeutic Antibodies ◽  
Plasma Therapy ◽  
Host Immune Responses ◽  
Transparent Liquid

Hitherto, there is no proper line of treatment for the new (nCOVID19). The development of unique antiviral drugs has taken precedence. Therapeutic antibodies () will be a significantly beneficial agent against nCOVID-19. Here the host immune responses to new discussed in this review provide strategy and further treatment and understanding of clinical interventions against nCOVID-19. Plasma therapy uses the antibodies found in the blood of people recovering (or convalesced) from an infection to treat infected patients. When an infection occurs, the body begins producing proteins specially made to kill the germ, called antibodies. Those antibodies coat specifically plasma in the blood of survivors, the yellow transparent liquid blood portion for months or even years. research assesses plasma use from Convalescent patients of infected with nCOVID-19 as a possible preventive treatment. But it is not yet recommended as a line of treatment, and it is used as a clinical trial in the new in Indian population.

scholarly journals Role of Alternative Splicing in Regulating Host Response to Viral Infection

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1720
Author(s):  
Kuo-Chieh Liao ◽  
Mariano A. Garcia-Blanco
Keyword(s):  
Innate Immunity ◽  
Alternative Splicing ◽  
Immune Responses ◽  
Viral Infection ◽  
Rna Splicing ◽  
Type I ◽  
Host Immune Responses ◽  
Transcriptional Regulatory Mechanisms ◽  
Host Virus Interactions

The importance of transcriptional regulation of host genes in innate immunity against viral infection has been widely recognized. More recently, post-transcriptional regulatory mechanisms have gained appreciation as an additional and important layer of regulation to fine-tune host immune responses. Here, we review the functional significance of alternative splicing in innate immune responses to viral infection. We describe how several central components of the Type I and III interferon pathways encode spliced isoforms to regulate IFN activation and function. Additionally, the functional roles of splicing factors and modulators in antiviral immunity are discussed. Lastly, we discuss how cell death pathways are regulated by alternative splicing as well as the potential role of this regulation on host immunity and viral infection. Altogether, these studies highlight the importance of RNA splicing in regulating host–virus interactions and suggest a role in downregulating antiviral innate immunity; this may be critical to prevent pathological inflammation.

scholarly journals β-Catenin Is Required for the cGAS/STING Signaling Pathway but Antagonized by the Herpes Simplex Virus 1 US3 Protein

2019 ◽  
Vol 94 (5) ◽  
Author(s):  
Hongjuan You ◽  
Yingying Lin ◽  
Feng Lin ◽  
Mingyue Yang ◽  
Jiahui Li ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Herpes Simplex ◽  
Immune Responses ◽  
Signaling Pathway ◽  
Kinase Activity ◽  
Dna Virus ◽  
Host Immune Responses ◽  
Simplex Virus ◽  
Antiviral Innate Immunity ◽  
Hsv 1

ABSTRACT The cGAS/STING-mediated DNA-sensing signaling pathway is crucial for interferon (IFN) production and host antiviral responses. Herpes simplex virus I (HSV-1) is a DNA virus that has evolved multiple strategies to evade host immune responses. Here, we demonstrate that the highly conserved β-catenin protein in the Wnt signaling pathway is an important factor to enhance the transcription of type I interferon (IFN-I) in the cGAS/STING signaling pathway, and the production of IFN-I mediated by β-catenin was antagonized by HSV-1 US3 protein via its kinase activity. Infection by US3-deficienct HSV-1 and its kinase-dead variants failed to downregulate IFN-I and IFN-stimulated gene (ISG) production induced by β-catenin. Consistent with this, absence of β-catenin enhanced the replication of US3-deficienct HSV-1, but not wild-type HSV-1. The underlying mechanism was the interaction of US3 with β-catenin and its hyperphosphorylation of β-catenin at Thr556 to block its nuclear translocation. For the first time, HSV-1 US3 has been shown to inhibit IFN-I production through hyperphosphorylation of β-catenin and to subvert host antiviral innate immunity. IMPORTANCE Although increasing evidence has demonstrated that HSV-1 subverts host immune responses and establishes lifelong latent infection, the molecular mechanisms by which HSV-1 interrupts antiviral innate immunity, especially the cGAS/STING-mediated cellular DNA-sensing signaling pathway, have not been fully explored. Here, we show that β-catenin promotes cGAS/STING-mediated activation of the IFN pathway, which is important for cellular innate immune responses and intrinsic resistance to DNA virus infection. The protein kinase US3 antagonizes the production of IFN by targeting β-catenin via its kinase activity. The findings in this study reveal a novel mechanism for HSV-1 to evade host antiviral immunity and add new knowledge to help in understanding the interaction between the host and HSV-1 infection.

scholarly journals Essential role of IRAK-4 protein and its kinase activity in Toll-like receptor–mediated immune responses but not in TCR signaling

2007 ◽  
Vol 204 (5) ◽  
pp. 1013-1024 ◽  
Author(s):  
Tatsukata Kawagoe ◽  
Shintaro Sato ◽  
Andreas Jung ◽  
Masahiro Yamamoto ◽  
Kosuke Matsui ◽  
...  
Keyword(s):  
Immune Responses ◽  
Kinase Activity ◽  
Interleukin 1 ◽  
Cell Receptor ◽  
Nuclear Factor Κb ◽  
Toll Like Receptor ◽  
Tcr Signaling ◽  
Mitogen Activated Protein

Interleukin-1 receptor–associated kinase 4 (IRAK-4) was reported to be essential for the Toll-like receptor (TLR)– and T cell receptor (TCR)–mediated signaling leading to the activation of nuclear factor κB (NF-κB). However, the importance of kinase activity of IRAK family members is unclear. In this study, we investigated the functional role of IRAK-4 activity in vivo by generating mice carrying a knockin mutation (KK213AA) that abrogates its kinase activity. IRAK-4KN/KN mice were highly resistant to TLR-induced shock response. The cytokine production in response to TLR ligands was severely impaired in IRAK-4KN/KN as well as IRAK-4−/− macrophages. The IRAK-4 activity was essential for the activation of signaling pathways leading to mitogen-activated protein kinases. TLR-induced IRAK-4/IRAK-1–dependent and –independent pathways were involved in early induction of NF-κB–regulated genes in response to TLR ligands such as tumor necrosis factor α and IκBζ. In contrast to a previous paper (Suzuki, N., S. Suzuki, D.G. Millar, M. Unno, H. Hara, T. Calzascia, S. Yamasaki, T. Yokosuka, N.J. Chen, A.R. Elford, et al. 2006. Science. 311:1927–1932), the TCR signaling was not impaired in IRAK-4−/− and IRAK-4KN/KN mice. Thus, the kinase activity of IRAK-4 is essential for the regulation of TLR-mediated innate immune responses.

scholarly journals Inflammasomes inMycobacterium tuberculosis-Driven Immunity

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Sebastian Wawrocki ◽  
Magdalena Druszczynska
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Inflammatory Response ◽  
Immune Responses ◽  
Proinflammatory Cytokines ◽  
Immune Cells ◽  
Protein Complexes ◽  
Inflammasome Activation ◽  
Host Immune Responses ◽  
Multimeric Protein

The development of effective innate and subsequent adaptive host immune responses is highly dependent on the production of proinflammatory cytokines that increase the activity of immune cells. The key role in this process is played by inflammasomes, multimeric protein complexes serving as a platform for caspase-1, an enzyme responsible for proteolytic cleavage of IL-1βand IL-18 precursors. Inflammasome activation, which triggers the multifaceted activity of these two proinflammatory cytokines, is a prerequisite for developing an efficient inflammatory response against pathogenicMycobacterium tuberculosis(M.tb). This review focuses on the role of NLRP3 and AIM2 inflammasomes inM.tb-driven immunity.

scholarly journals Antibiotics in early life and childhood pre-B-ALL. Reasons to analyze a possible new piece in the puzzle

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
T. M. Cardesa-Salzmann ◽  
A. Simon ◽  
N. Graf
Keyword(s):  
Immune Responses ◽  
Early Life ◽  
Lymphoblastic Leukemia ◽  
Antibiotic Use ◽  
Intestinal Microbiome ◽  
Microbial Composition ◽  
Hematopoietic Stem ◽  
Childhood All ◽  
Host Immune Responses

AbstractAcute lymphoblastic leukemia (ALL) is the most common pediatric cancer with precursor B-cell ALL (pB-ALL) accounting for ~ 85% of the cases. Childhood pB-ALL development is influenced by genetic susceptibility and host immune responses. The role of the intestinal microbiome in leukemogenesis is gaining increasing attention since Vicente-Dueñas’ seminal work demonstrated that the gut microbiome is distinct in mice genetically predisposed to ALL and that the alteration of this microbiome by antibiotics is able to trigger pB-ALL in Pax5 heterozygous mice in the absence of infectious stimuli. In this review we provide an overview on novel insights on the role of the microbiome in normal and preleukemic hematopoiesis, inflammation, the effect of dysbiosis on hematopoietic stem cells and the emerging importance of the innate immune responses in the conversion from preleukemic to leukemic state in childhood ALL. Since antibiotics, which represent one of the most widely used medical interventions, alter the gut microbial composition and can cause a state of dysbiosis, this raises exciting epidemiological questions regarding the implications for antibiotic use in early life, especially in infants with a a preleukemic “first hit”. Sheading light through a rigorous study on this piece of the puzzle may have broad implications for clinical practice.

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