The role of IL-9 signaling in pulmonary Francisella infection

dc.contributor.advisorArulanandam, Bernard P.
dc.contributor.authorDoelger, Richard
dc.contributor.committeeMemberGuentzel, Neal
dc.contributor.committeeMemberChambers, James P.
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dc.description.abstractFrancisella tularensis (F. tularensis) is a facultative intracellular Gram-negative bacterium that is the causative agent of pulmonary tularemia infections. The ability of current vaccines to protect the host against F. tularensis Type A Schu S4 is incomplete and unsuitable for human use according to the FDA. Our lab has previously established an in vitro mast-cell and macrophage co-culture system to evaluate the effect of mast cell secreted factors on macrophage-mediated bacterial killing to control F. tularensis infection. There is a piece of evidence which shows that stimulation of macrophages with mast cell IL-4 enhanced bacterial killing. In contrast, addition of exogenous rIL-9 to mast-cell-macrophage co-culture resulted in decrease of mast cell IL-4 production and increase of F. tularensis replication in macrophages. I hypothesize that IL-9 plays a role in controlling bacterial burdens during the primary stage of infection. A IL-9R deficient mouse was used to compare with IL-9R sufficient wild type mice in susceptible to pulmonary F. tularensis Live Vaccine Strain (LVS) challenge. We demonstrate that abrogation of IL9 signaling resulted in decreased bacterial burdens and improved efficacy of the immune system to eliminate Francisella. The cytokines IL-9, IL4 and TGF-β that are involved in immune defenses against LVS infection exhibit different expression patterns in the lungs of IL9R deficient (IL9R-/- ) mice correlating with differential immune cell (T cells, macrophages and other PMNs) infiltration to the infection site.
dc.description.departmentIntegrative Biology
dc.format.extent38 pages
dc.subject.lcshFrancisella tularensis
dc.subject.lcshLungs -- Infections -- Treatment
dc.titleThe role of IL-9 signaling in pulmonary Francisella infection
dcterms.accessRightspq_closed Biology of Texas at San Antonio of Science


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