Reversing Post-Infectious Epigenetic-Mediated Immune Suppression

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dc.citation.articleNumber688132en_US
dc.citation.journalTitleFrontiers in Immunologyen_US
dc.citation.volumeNumber12en_US
dc.contributor.authorAbhimanyuen_US
dc.contributor.authorOntiveros, Carlos O.en_US
dc.contributor.authorGuerra-Resendez, Rosa S.en_US
dc.contributor.authorNishiguchi, Tomokien_US
dc.contributor.authorLadki, Maliken_US
dc.contributor.authorHilton, Isaac B.en_US
dc.contributor.authorSchlesinger, Larry S.en_US
dc.contributor.authorDiNardo, Andrew R.en_US
dc.contributor.orgSystems, Synthetic, and Physical Biology Programen_US
dc.date.accessioned2021-07-08T13:46:03Zen_US
dc.date.available2021-07-08T13:46:03Zen_US
dc.date.issued2021en_US
dc.description.abstractEpigenetic changes limit the immune response from inducing exuberant collateral damage to host tissue after severe and chronic infections. However, following treatment for these infections, including sepsis, pneumonia, hepatitis B, hepatitis C, HIV, tuberculosis (TB) or schistosomiasis, detrimental epigenetic scars persist, and result in long-lasting immune suppression. This is believed to be one of the contributing factors for why survivors of infection have increased all-cause mortality and increased rates of unrelated secondary infections. Several mechanisms that induce epigenetic-mediated immune suppression have been demonstrated in-vitro and in animal models. Modulation of the AMPK-mTOR, NFAT or NR4A pathways is able to block or reverse the development of detrimental epigenetic scars. Similarly, drugs that directly modify epigenetic enzymes, such as those that inhibit histone deacetylase (HDAC) inhibitors, DNA hypomethylating agents or modifiers of the Nucleosome Remodeling and DNA methylation (NuRD) complex or Polycomb Repressive Complex (PRC) have demonstrated capacity to restore host immunity in the setting of cancer-, LCMV- or murine sepsis-induced epigenetic-mediated immune suppression. A third clinically feasible strategy for reversing detrimental epigenetic scars are bioengineering approaches to either directly reverse the detrimental epigenetic marks or to modify the epigenetic enzymes or transcription factors that induce detrimental epigenetic scars. Each of these approaches, alone or in combination, have ablated or reversed detrimental epigenetic marks in in-vitro or in animal models; translational studies are now required to evaluate clinical applicability.en_US
dc.identifier.citationAbhimanyu, Ontiveros, Carlos O., Guerra-Resendez, Rosa S., et al.. "Reversing Post-Infectious Epigenetic-Mediated Immune Suppression." <i>Frontiers in Immunology,</i> 12, (2021) Frontiers Media S.A.: https://doi.org/10.3389/fimmu.2021.688132.en_US
dc.identifier.digitalfimmu-12-688132en_US
dc.identifier.doihttps://doi.org/10.3389/fimmu.2021.688132en_US
dc.identifier.urihttps://hdl.handle.net/1911/111001en_US
dc.language.isoengen_US
dc.publisherFrontiers Media S.A.en_US
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleReversing Post-Infectious Epigenetic-Mediated Immune Suppressionen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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