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dc.contributor.authorSmith-Page, Kirsten
dc.date.accessioned2019-12-10T11:15:47Z
dash.embargo.terms2020-05-01
dc.date.created2019-11
dc.date.issued2019-10-09
dc.date.submitted2019
dc.identifier.citationSmith-Page, Kirsten. 2019. Commensals Modulate Innate Immune Response Through L-Plastin to Bacterial Keratitis. Master's thesis, Harvard Extension School.
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:42006724*
dc.description.abstractL-plastin (LPL) is implicated in regulating innate and adaptive immune responses. Previous work showed that the ocular surface proteomes of Specific Pathogen Free mice had high levels of LPL and neutrophil secreted peptides when compared to the proteomes of Germ Free mice, suggesting that LPL contributed to the responses to commensals, and the response was neutrophil dependent. My goal was to establish conditional knockout mouse strains to assess the role of LPL in different myeloid compartments with respect to susceptibility to bacterial keratitis, identify ocular commensal presence and response of the innate immune cells to commensal sensitization. Comparison of P. aeruginosa susceptibility in LPL conditional knock out mice with specific ablation of LPL under the promoters of LysM Cre (LysM LPL KO), CX3CR1 (CX3CR1 LPL KO)and S100A8 (S100A8 LPL KO) was determined. Both LysM LPL KO and S100 A8 LPL KO mice displayed conjunctival lactic acid bacteria commensal differences in timeline experiments and increased susceptibility to P. aeruginosa-induced keratitis (p=0.0049 and 0.03, respectively). Medium from macrophage training experiments with and without the lactic acid producing commensal, S. ovis, was added to P. aeruginosa challenged PMNs to determine commensal sensitization potential and effect of LPL deficiency on bactericidal activity. Macrophage training inhibited neutrophil bactericidal activity and LPL deficient PMNs had marked reduced killing as compared with wild type. Together these results show that L-plastin controls neutrophil functionality and commensals modulate neutrophil response through macrophage commensal cross-talk and pathogen susceptibility.
dc.description.sponsorshipBioengineering & Nanotechnology
dc.format.mimetypeapplication/pdf
dash.licenseLAA
dc.subjectinnate immune response on ocular surface
dc.subjectcommensal profile
dc.subjectbacterial keratitis
dc.subjectL-plastin
dc.subjectcommensal training of macrophages
dc.subjectStreptococcus acidominimus, Streptococcus ovis
dc.titleCommensals Modulate Innate Immune Response Through L-Plastin to Bacterial Keratitis
dc.typeThesis or Dissertation
dash.depositing.authorSmith-Page, Kirsten
dash.embargo.until2020-05-01
dc.date.available2019-12-10T11:15:47Z
thesis.degree.date2019
thesis.degree.grantorHarvard Extension School
thesis.degree.grantorHarvard Extension School
thesis.degree.levelMasters
thesis.degree.levelMasters
thesis.degree.nameALM
thesis.degree.nameALM
dc.contributor.committeeMemberDenkin, Steven
dc.contributor.committeeMemberGadjeva, Mihaela
dc.type.materialtext
thesis.degree.departmentBioengineering & Nanotechnology
thesis.degree.departmentBioengineering & Nanotechnology
dash.identifier.vireo
dash.author.emailkirsten.page@cocmast.net


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