Schistosomiasis Induces Persistent DNA Methylation and Tuberculosis-Specific Immune Changes

The Journal of Immunology : Official Journal of the American Association of Immunologists
Andrew R DiNardoGeorge Makedonas

Abstract

Epigenetic mechanisms, such as DNA methylation, determine immune cell phenotype. To understand the epigenetic alterations induced by helminth coinfections, we evaluated the longitudinal effect of ascariasis and schistosomiasis infection on CD4+ T cell DNA methylation and the downstream tuberculosis (TB)-specific and bacillus Calmette-Guérin-induced immune phenotype. All experiments were performed on human primary immune cells from a longitudinal cohort of recently TB-exposed children. Compared with age-matched uninfected controls, children with active Schistosoma haematobium and Ascaris lumbricoides infection had 751 differentially DNA-methylated genes, with 72% hypermethylated. Gene ontology pathway analysis identified inhibition of IFN-γ signaling, cellular proliferation, and the Th1 pathway. Targeted real-time quantitative PCR after methyl-specific endonuclease digestion confirmed DNA hypermethylation of the transcription factors BATF3, ID2, STAT5A, IRF5, PPARg, RUNX2, IRF4, and NFATC1 and cytokines or cytokine receptors IFNGR1, TNFS11, RELT (TNF receptor), IL12RB2, and IL12B (p < 0.001; Sidak-Bonferroni). Functional blockage of the IFN-γ signaling pathway was confirmed, with helminth-infected individuals having decreased up...Continue Reading

Associated Clinical Trials

References

Mar 8, 2003·Revista Da Sociedade Brasileira De Medicina Tropical·Ricardo Tristão-SáReynaldo Dietze
Mar 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Meghan E PenniniClifford V Harding
Mar 24, 2006·Tropical Medicine & International Health : TM & IH·Daniel EliasSven Britton
Aug 22, 2007·The Journal of Experimental Medicine·James P Scott-BrowneKevin B Urdahl
Apr 3, 2008·The Journal of Clinical Investigation·Peter J HotezJulie Jacobson
Jun 24, 2008·Epigenetics : Official Journal of the DNA Methylation Society·Ben Youngblood, Norbert O Reich
Jul 29, 2009·The Journal of Experimental Medicine·Bart EvertsGabriele Schramm
Sep 30, 2010·The Journal of Experimental Medicine·John R GraingerRick M Maizels
Oct 5, 2010·American Journal of Respiratory Cell and Molecular Biology·Seónadh O'LearyJoseph Keane
May 7, 2011·Bioinformatics·Arthur LiberzonJill P Mesirov
May 19, 2011·PLoS Pathogens·Judith E Allen, Thomas A Wynn
Jun 2, 2011·Genome Research·Aimée M DeatonAdrian Bird
Oct 8, 2011·Immunology·Kiyoshi HiraharaArian Laurence
Jan 17, 2012·Trends in Parasitology·Eyrun F KjetlandPatricia D Ndhlovu
Mar 1, 2012·PLoS Pathogens·Andrzej PawlowskiGunilla Källenius
Jun 14, 2012·The International Journal of Tuberculosis and Lung Disease : the Official Journal of the International Union Against Tuberculosis and Lung Disease·A M MandalakasA C Hesseling
Sep 19, 2012·Proceedings of the National Academy of Sciences of the United States of America·Johanneke KleinnijenhuisMihai G Netea
Jan 8, 2013·International Journal for Parasitology·Henry J McSorleyRick M Maizels
Jun 19, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ben YoungbloodDaniel E Kaufmann
Jul 6, 2013·Nature Reviews. Immunology·William C GauseJudith E Allen
Jul 9, 2014·The Journal of Infectious Diseases·Kaori Nakayama-HosoyaAi Kawana-Tachikawa
Jul 25, 2014·PLoS Neglected Tropical Diseases·Peter J HotezMohsen Naghavi
Aug 5, 2014·Epigenetics : Official Journal of the DNA Methylation Society·Breezy M LindqvistTorbjörn K Nilsson
Dec 30, 2014·Nucleic Acids Research·Ramon M RodriguezCarlos Lopez-Larrea

❮ Previous
Next ❯

Citations

Jan 10, 2020·Epigenetics : Official Journal of the DNA Methylation Society·Samantha BannisterNigel Curtis
Mar 4, 2020·The Journal of Clinical Investigation·Andrew R DiNardoAnna M Mandalakas
Jul 12, 2019·Frontiers in Pediatrics·Elizabeth WhittakerJames A Seddon
Aug 14, 2020·Scientific Reports·Marcelo B SzteinRosângela Salerno-Goncalves
Nov 5, 2019·Frontiers in Immunology·Jayne Louise WilsonThomas Weichhart
Jan 21, 2021·The New England Journal of Medicine·Andrew R DiNardoDaniel M Musher
Sep 17, 2019·Heart, Lung & Circulation·Ezzeldin A MostafaZeinab A Kamar
Mar 7, 2021·Nutrients·Nathalie AcevedoBetty C A M van Esch
Jun 25, 2021·Frontiers in Immunology· AbhimanyuAndrew R DiNardo
Jul 17, 2021·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Aline Marrara PradoFernanda Janku Cabral
Jul 10, 2021·Pediatric Research·Jennifer Bermick, Matthew Schaller

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Biology: Molecular Imaging

Molecular imaging enables noninvasive imaging of key molecules that are crucial to tumor biology. Discover the latest research in molecular imaging in cancer biology in this feed.

Cell Signaling & Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. This feed covers the latest research on signaling and epigenetics in cell growth and cancer.

Ascariasis (ASM)

Ascariasis is a helminthic infection of global distribution with more than 1.4 billion persons infected throughout the world. Here is the latest research.

Anthelmintics (ASM)

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.

Ascariasis

Ascariasis is a helminthic infection of global distribution with more than 1.4 billion persons infected throughout the world. Here is the latest research.

CD4/CD8 Signaling

Cluster of differentiation 4 and 8 (CD8 and CD8) are glycoproteins founds on the surface of immune cells. Here is the latest research on their role in cell signaling pathways.

Anthelmintics

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.

Related Papers

BioRxiv : the Preprint Server for Biology
Andrew R DiNardoAnna M Mandalakas
The Journal of Clinical Investigation
Andrew R DiNardoAnna M Mandalakas
BioRxiv : the Preprint Server for Biology
Andrew R DiNardoAnna M Mandalakas
Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc
Anshu AgrawalDevendra K Agrawal
© 2022 Meta ULC. All rights reserved