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dc.contributor.advisorBriken, Volkeren_US
dc.contributor.authorAhlbrand, Sarahen_US
dc.date.accessioned2018-01-23T06:37:28Z
dc.date.available2018-01-23T06:37:28Z
dc.date.issued2017en_US
dc.identifierdoi:10.13016/M2B56D62C
dc.identifier.urihttp://hdl.handle.net/1903/20323
dc.description.abstractNumerous cytokines are induced as a consequence of infection by Mycobacterium tuberculosis (Mtb), an intracellular pathogen that is responsible for millions of deaths each year. These cytokines play varied roles in eliciting and regulating the innate and adaptive immune responses against Mtb and often determine disease outcome. The pro-inflammatory cytokine interleukin 1β (IL-1β) is required for Mtb maintenance and clearance, as mice lacking the ability to produce IL-1β succumb very quickly to infection compared to infected wildtype mice. In contrast, interferon β (IFNβ) is largely thought to be detrimental to the host during Mtb infection based on collective studies in patients and mouse models. Both IL-1β and IFNβ are induced during Mtb infection, but here we demonstrate that Mtb has also evolved mechanisms to reduce their production and/or signaling. Previously, we’ve shown that Mtb can inhibit IL-1β production induced by the Absent in Melanoma 2 (AIM2) inflammasome. These findings were expanded upon by investigating the mechanisms by which Mtb inhibits AIM2 activation. A gain-of-function screen was also utilized in the non-pathogenic mycobacterial species Msmeg to identify Mtb genomic regions contributing to this phenomenon. In addition, we demonstrate that Mtb inhibits IFNβ signaling by inhibiting IFNβ-induced JAK1 and Tyk2 phosphorylation, leading to changes in the host type I interferon transcriptional profile. These studies provide insight into two previously undescribed mechanisms Mtb utilizes to manipulate the host immune response.en_US
dc.language.isoenen_US
dc.titleCHARACTERIZING THE INHIBITION OF INNATE IMMUNE SIGNALING BY MYCOBACTERIUM TUBERCULOSISen_US
dc.typeDissertationen_US
dc.contributor.publisherDigital Repository at the University of Marylanden_US
dc.contributor.publisherUniversity of Maryland (College Park, Md.)en_US
dc.contributor.departmentMolecular and Cell Biologyen_US
dc.subject.pqcontrolledMicrobiologyen_US
dc.subject.pqcontrolledImmunologyen_US
dc.subject.pqcontrolledCellular biologyen_US
dc.subject.pquncontrolledCytokineen_US
dc.subject.pquncontrolledHost/Pathogen Interactionsen_US
dc.subject.pquncontrolledInnate Immunityen_US
dc.subject.pquncontrolledMycobacterium tuberculosisen_US


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