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dc.contributor.advisorChairperson, Graduate Committee: Jovanka Voyich-Kaneen
dc.contributor.authorZurek, Oliwia Wiktoriaen
dc.contributor.otherTyler K. Nygaard, Robert L. Watkins, Kyler B. Pallister, Victor J. Torres, Alexander R. Horswill and Jovanka M. Voyich were co-authors of the article, 'The role of innate immunity in promoting SAER/S-mediated virulence in Staphylococcus aureus' in the journal 'Journal of innate immunity' which is contained within this thesis.en
dc.contributor.otherKyler B. Pallister and Jovanka M. Voyich were co-authors of the article, 'Staphylococcus aureus inhibits neutrophil-derived IL-8 to promote cell death' in the journal 'Journal of Infectious Diseases' which is contained within this thesis.en
dc.date.accessioned2017-01-21T17:49:41Z
dc.date.available2017-01-21T17:49:41Z
dc.date.issued2015en
dc.identifier.urihttps://scholarworks.montana.edu/xmlui/handle/1/10150
dc.description.abstractStaphylococcus aureus (S. aureus) is a highly adaptable pathogen that can cause endocarditis, skin abscesses, tissue necrosis, and sepsis. S. aureus success can be partially attributed to its ability to colonize and subsequently infect a wide variety of host tissues. This capacity is dependent on elaborate two-component gene-regulatory systems that control expression of virulence and immunomodulatory factors. The S. aureus exoprotein expression (SaeR/S) system is recognized as a major regulator of virulence that significantly contributes to the pathogen's ability to evade killing by the human neutrophil. However, it is unclear how this system becomes activated and how the SaeR/S system modulates neutrophil function. In this study, we elucidated how S. aureus evades neutrophil killing by studying the reciprocal communication between the host and pathogen. We demonstrated that only select SaeR/S-regulated genes (as opposed to all targets) were transcriptionally up-regulated in response to stimulation by neutrophils as well as alpha-defensin and show that the mouse skin environment (that lacks alpha-defensin) promoted transcription of specific saeR/S-targets, different from the expression profile elicited following neutrophil interaction or alpha-defensin. These results were unexpected and demonstrated differential activation of saeR/S targets was dependent on specific stimuli. Furthermore, we studied the influence of SaeR/S on neutrophil function and showed that this system promoted accelerated cell death by decreasing NF-kB activity, and in-turn IL- 8 production, to promote neutrophil lysis. These findings underscored the importance of neutrophil signaling demonstrating that neutrophil-derived production of IL-8 was necessary for this cell to kill S. aureus effectively. It follows that treatment of human neutrophils with recombinant IL-8 significantly increased neutrophil staphylocidal activity. Finally, we propose that both timing and magnitude of inflammation in neutrophils play major roles in dictating the outcome of staphylococcal disease and that alteration in the innate ability of neutrophils to produce IL-8 may increase susceptibility to S. aureus infections. Taken together, the findings define novel pathogen- and host-derived factors that play pivotal roles in the course of S. aureus infection.en
dc.language.isoenen
dc.publisherMontana State University - Bozeman, College of Letters & Scienceen
dc.subject.lcshNeutrophils.en
dc.subject.lcshStaphylococcus aureus.en
dc.subject.lcshMolecular geneticsen
dc.subject.lcshImmune response.en
dc.titleInsights into the reciprocal communication between Neutrophils and Staphylococcus aureusen
dc.typeDissertationen
dc.rights.holderCopyright 2015 by Oliwia Wiktoria Zurek.en
thesis.degree.committeemembersMembers, Graduate Committee: Jovanka Voyich-Kane (chairperson); Michele Hardy; Mark Jutila; Mark T. Quinn; Wendy A. Stock.en
thesis.degree.departmentMicrobiology & Immunology.en
thesis.degree.genreDissertationen
thesis.degree.namePhDen
thesis.format.extentfirstpage1en
thesis.format.extentlastpage98en
mus.relation.universityMontana State University - Bozemanen_US
mus.data.thumbpage46


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