Targeting the toll-like receptor pathway as a therapeutic strategy for neonatal infection

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dc.contributor.authorDias, Maria L.
dc.contributor.authorO'Connor, Karen M.
dc.contributor.authorDempsey, Eugene M.
dc.contributor.authorO'Halloran, Ken D.
dc.contributor.authorMcDonald, Fiona B.
dc.date.accessioned2021-10-11T11:28:24Z
dc.date.available2021-10-11T11:28:24Z
dc.date.issued2021-10-06
dc.date.updated2021-10-11T11:17:17Z
dc.description.abstractToll-like receptors (TLRs) are crucial transmembrane receptors that form part of the innate immune response. They play a role in the recognition of various microorganisms and their elimination from the host. TLRs have been proposed as vital immunomodulators in the regulation of multiple neonatal stressors that extend beyond infection such as oxidative stress and pain. The immune system is immature at birth and takes some time to become fully established. As such, babies are especially vulnerable to sepsis at this early stage of life. Findings suggest a gestational age-dependent increase in TLR expression. TLRs engage with accessory and adaptor proteins to facilitate recognition of pathogens and their activation of the receptor. TLRs are generally upregulated during infection and promote the transcription and release of proinflammatory cytokines. Several studies report that TLRs are epigenetically modulated by chromatin changes and promoter methylation upon bacterial infection which have long-term influences on immune responses. TLR activation is reported to modulate cardiorespiratory responses during infection and may play a key role in driving homeostatic instability observed during sepsis. Although complex, TLR signalling and downstream pathways are potential therapeutic targets in the treatment of neonatal diseases. By reviewing the expression and function of key toll-like receptors, we aim to provide an important framework to understand the functional role of these receptors in response to stress and infection in premature infants.en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationDias, M. L., O'Connor, K. M., Dempsey, E., O'Halloran, K. D. and McDonald, F. B. (2021) 'Targeting the toll-like receptor pathway as a therapeutic strategy for neonatal infection', American Journal of Physiology - Regulatory, Integrative and Comparative Physiology. doi: 10.1152/ajpregu.00307.2020en
dc.identifier.doi10.1152/ajpregu.00307.2020en
dc.identifier.issn1522-1490
dc.identifier.issn0002-9513
dc.identifier.journaltitleAmerican Journal of Physiology - Regulatory, Integrative and Comparative Physiologyen
dc.identifier.urihttps://hdl.handle.net/10468/12080
dc.language.isoenen
dc.publisherAmerican Physiological Societyen
dc.rights© 2021, the Authors. Licensed under Creative Commons Attribution CC-BY 4.0.Published by the American Physiological Society.R879Am J Physiol Regul Integr Comp Physiol 321: R879–R902, 2021.First published October 6, 2021; doi:10.1152/ajpregu.00307.2020en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectInflammationen
dc.subjectSepsisen
dc.subjectEarly lifeen
dc.subjectPretermen
dc.subjectCardiorespiratoryen
dc.titleTargeting the toll-like receptor pathway as a therapeutic strategy for neonatal infectionen
dc.typeArticle (peer-reviewed)en
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