Toll-like Receptor 2 Mediates the Host's Responses in Murine Respiratory Mycoplasmosis

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dc.contributor.advisorJerry W. Simecka
dc.contributor.committeeMemberDuncan C. Krause
dc.contributor.committeeMemberStephen R. Grant
dc.creatorLove, Wees JaMar
dc.date.accessioned2019-08-22T21:30:57Z
dc.date.available2019-08-22T21:30:57Z
dc.date.issued2008-04-01
dc.date.submitted2013-09-23T12:42:08-07:00
dc.description.abstractLove, Wees J., The role of Toll-like receptor 2 in mediating the host’s defenses toward mycoplasma infection in the upper and lower respiratory tracts. Doctor of Philosophy (Microbiology and Immunology), April, 2008, 88 pp., 7 illustrations, bibliography, 144 titles. The purpose of these studies was to investigate the toll-like receptors (TLR) responsible for the recognition of invading mycoplasmas. They were also meant to evaluate the role of Toll-like receptors in the generation of immune responses and disease progression in mycoplasma respiratory disease. To determine the role of TLRs in recognizing viable Mycoplasma pulmonis, we utilized human embryonic kidney (HEK) cell lines that are known to have low basal expression of TLRs. The HEK cell lines used were stably transfected to express various combinations of TLRs. The HEK cell lines used were stably transfected to express various combinations of TLRs including TLR1, 2 and 6. The current paradigm of TLR recognition of mycoplasma is that TLR2 dimerizes with either TLR1 or TLR6 to recognize different subclasses of mycoplasma lipoproteins. However, the recognition of viable M. pulmonis organisms remains unclear. When stimulated with viable M. pulmonis, it was discovered that TLR2 was pivotal in mediating the host’s pro-inflammatory cytokine production and that the co-expression of TLR1 or TLR6 enhanced the response. To study their role in mycoplasma recognition and disease progression, we utilized TLR2 knockout (KO) mice. Bone-marrow derived dendritic cells (BMDC) from TLR2 KO mice showed an impaired ability to produce pro-inflammatory cytokines such as IL-12p40 in response to viable M. pulmonis. In addition, the host’s ability to clear the infection was also impaired in TLR2 KO animals. There were higher numbers of cfu in the lower respiratory tract where alveolar macrophages are known to mediate the host’s intrapulmonary clearance of organism. In the upper respiratory tract, where alveolar macrophages (AM) are absent, the production of anti-microbial peptides (e.g. β defensing) in response to TLR2 agonists has been demonstrated. Thus, TLR2 does mediate the host’s immune response to mycoplasma infection, by interfering with the host’s ability to clear the infection and be interfering with the host’s ability to mount an effective inflammatory response. These results also suggest that the TLR2 mediated anti-mycoplasma effects vary and are compartmentalized along the respiratory tract. These studies demonstrated diverse and novel roles of TLRs in respiratory infections and will serve as a platform for future studies investigating mycoplasma respiratory infections.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/20.500.12503/29389
dc.language.isoen
dc.provenance.legacyDownloads1
dc.subjectCell and Developmental Biology
dc.subjectCell Biology
dc.subjectImmunity
dc.subjectImmunology and Infectious Disease
dc.subjectImmunopathology
dc.subjectLife Sciences
dc.subjectMedical Cell Biology
dc.subjectMedicine and Health Sciences
dc.subjectRespiratory System
dc.subjectRespiratory Tract Diseases
dc.subjectToll-like receptor 2
dc.subjectmycoplasma infection
dc.subjectupper and lower respiratory tracts
dc.subjectTLR
dc.subjectmycoplasma pulmonis
dc.subjecthuman embryonic kidney
dc.subjectTLR2 knockout mice
dc.subjectBone-marrow derived dendritic cells
dc.subjectpro-inflammatory cytokines
dc.subjectimmune response
dc.subjectrespiratory infections
dc.titleToll-like Receptor 2 Mediates the Host's Responses in Murine Respiratory Mycoplasmosis
dc.typeDissertation
dc.type.materialtext
thesis.degree.departmentGraduate School of Biomedical Sciences
thesis.degree.disciplineMicrobiology and Immunology
thesis.degree.grantorUniversity of North Texas Health Science Center at Fort Worth
thesis.degree.nameDoctor of Philosophy

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