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You searched for +publisher:"University of Manitoba" +contributor:("GOUNNI, Abdelilah SOUSSI (Immunology)"). Showing records 1 – 3 of 3 total matches.

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University of Manitoba

1. Jaggupilli, Appalaraju. Chemosensory mechanisms of bitter taste receptors (T2Rs) in mediating host-pathogen interactions in airways.

Degree: Oral Biology, 2018, University of Manitoba

Bitter taste receptors (T2Rs) belong to G protein-coupled receptor superfamily. In humans, 25 T2Rs perform a chemosensory function with little information on their extraoral role. Recent studies suggest the expression of T2Rs in different tissues and their interaction with quorum-sensing molecules (QSMs). This thesis has two independent hypotheses involving T2Rs: First hypothesis, human airways show differential expression of T2Rs in pathophysiological conditions such as cystic fibrosis (CF). The second hypothesis, bacterial QSMs and bitter compounds mediate host-pathogen interactions through T2Rs in airways. To test these hypotheses, I analyzed the expression patterns of T2Rs at transcript and protein level in normal and CF airway cells. The results suggest a specific pattern of T2Rs with no differential expression in the samples analyzed. Next to assess T2R functionality, I pursued calcium mobilization assays after stimulation of cells with various bitter compounds. The inhibition of Gβγ-subunit and phospholipase-C (PLC) showed the calcium mobilized in these cells predominantly takes place through T2R-Gαβγ-PLC pathway. To test the second hypothesis, combination of molecular and pharmacological approaches were used to study the amino acid interactions in selected T2Rs. In these experiments, commonly used antibiotics in CF treatment, and major QSMs secreted by CF bacteria were tested. The results suggest that antibiotics and QSMs activate multiple T2Rs with different potencies. Extracellular loop-2 in T2Rs performs a key function in binding to the tested compounds. To address the lack of properly characterized bitter blockers, I pursued the characterization of novel T2R4 blockers derived from plant and meat products. A Schild regression analysis on the plant hormone abscisic acid determined its T2R4 antagonism as surmountable. Further testing with the naturally occuring (+)-ABA isomer indicated that individual isomers do not induce calcium mobilization. Subsequently, I identified and characterized advanced glycation end-products as T2R4 antagonists. Glyoxal-derived lysine dimer inhibited the quinine response while carboxy methyl lysate showed subtle inhibition. In conclusion, these structure-function and mechanistic studies on T2Rs identify as new targets for antibiotics and QSMs. This work provides new insights into the host-pathogen interactions in CF and may lead to novel therapeutic approaches for CF that target T2Rs. Advisors/Committee Members: Chelikani, Prashen (Oral Biology) (supervisor), Bhullar, Rajinder (Oral Biology) Duan, Kangmin (Oral Biology) Gounni, Abdelilah Soussi (Immunology) Dupre, Denis (Phamacology Dalhousie University) (examiningcommittee).

Subjects/Keywords: bitter taste receptors; cystic fibrosis; antibiotics; GPCR; quorum sensing

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Jaggupilli, A. (2018). Chemosensory mechanisms of bitter taste receptors (T2Rs) in mediating host-pathogen interactions in airways. (Thesis). University of Manitoba. Retrieved from http://hdl.handle.net/1993/33202

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Jaggupilli, Appalaraju. “Chemosensory mechanisms of bitter taste receptors (T2Rs) in mediating host-pathogen interactions in airways.” 2018. Thesis, University of Manitoba. Accessed October 22, 2019. http://hdl.handle.net/1993/33202.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Jaggupilli, Appalaraju. “Chemosensory mechanisms of bitter taste receptors (T2Rs) in mediating host-pathogen interactions in airways.” 2018. Web. 22 Oct 2019.

Vancouver:

Jaggupilli A. Chemosensory mechanisms of bitter taste receptors (T2Rs) in mediating host-pathogen interactions in airways. [Internet] [Thesis]. University of Manitoba; 2018. [cited 2019 Oct 22]. Available from: http://hdl.handle.net/1993/33202.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Jaggupilli A. Chemosensory mechanisms of bitter taste receptors (T2Rs) in mediating host-pathogen interactions in airways. [Thesis]. University of Manitoba; 2018. Available from: http://hdl.handle.net/1993/33202

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation


University of Manitoba

2. Omange, Robert Were. Toll-Like Receptor Responses in Peripheral Blood Mononuclear Cells of HIV Exposed Seronegative Female Commercial Sex Workers from Nairobi Kenya.

Degree: Medical Microbiology, 2016, University of Manitoba

The innate immune system is at the interface between the host's immune system and the initial contact with HIV. Understanding the correlates of innate immune protection against Human Immunodeficiency Virus is an important goal for development of effective anti-HIV therapies or vaccines. Not all exposures to HIV end in infection. The innate immune system has been linked to the reduced susceptibility of HIV-exposed seronegative (HESN) female commercial sex workers in Kenya by a number of studies. This thesis is a comparison of Toll-like receptor (TLR) responses in different immune cells in peripheral blood mononuclear cells (PBMCs) from HESN and HIV negative (susceptible) female commercial sex workers (CSWs). This study tested the hypothesis that higher TLR8 responsiveness in PBMCs of HESN to ssRNA analogous to HIV's genetic material, would result in higher effector responses capable of making HIV target cells more refractory in vitro, compared to susceptible controls. The results showed that PBMCs of HESN were often hypo-responsive to TLR4 and TLR7 stimulations evidenced by often reduced cytokine responses to the corresponding ligands, but hyper-responsive to TLR8 following stimulation with ssRNA analogous to HIV's genetic material. The 'dichotomy' in TLR responsiveness of HESN PBMCs was associated with differential expression of cognate TLRs in PBMCs, and altered activation of TLR signalling pathways. The opposing pattern of TLR7 and TLR8 responsiveness corresponded to the ability of HIV to infect target cells in vitro; where pre-treatment of PBMCs with TLR7 enhanced HIV replication whereas TLR8 stimulation inhibited HIV replication. The differences in outcomes of the HIV infection assays were associated with distinct cytokine profiles, where TLR7 stimulation induced robust type I IFNs responses without proinflammatory TNF-α and IL-12 cytokine responses,while TLR8 stimulations produced type II IFN responses accompanied by robust proinflammatory responses in both groups. The cytokine milieu of HESN PBMCs prior to and following TLR4 and TLR8 stimulations was more tightly regulated, but was associated with higher activation of CD8+, NK cells, monocytes but not blood DCs. These results demonstrate that the lower activation or 'quiescent' state of HESN PBMCs did not limit the ability of their cells to recognize ssRNA analogous to HIV derived genetic material and mount potent responses capable of limiting HIV infection in vitro, supporting the overall hypothesis tested. This thesis contributes to the growing knowledge on the dichotomous outcomes between TLR7 and TLR8 treatments with respect to HIV infection that could be instrumental in the design of novel HIV inventions such as vaccines or microbicides. Advisors/Committee Members: Ball, Terry Blake (Medical Microbiology/Immunology) (supervisor), Fowke, Keith R. (Medical Microbiology).

Subjects/Keywords: Toll-Like receptors; HIV exposed seronegative (HESN); HIV-N (HIV negatives); Innate Immunity; Dichotomous

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Omange, R. W. (2016). Toll-Like Receptor Responses in Peripheral Blood Mononuclear Cells of HIV Exposed Seronegative Female Commercial Sex Workers from Nairobi Kenya. (Thesis). University of Manitoba. Retrieved from http://hdl.handle.net/1993/31141

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Omange, Robert Were. “Toll-Like Receptor Responses in Peripheral Blood Mononuclear Cells of HIV Exposed Seronegative Female Commercial Sex Workers from Nairobi Kenya.” 2016. Thesis, University of Manitoba. Accessed October 22, 2019. http://hdl.handle.net/1993/31141.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Omange, Robert Were. “Toll-Like Receptor Responses in Peripheral Blood Mononuclear Cells of HIV Exposed Seronegative Female Commercial Sex Workers from Nairobi Kenya.” 2016. Web. 22 Oct 2019.

Vancouver:

Omange RW. Toll-Like Receptor Responses in Peripheral Blood Mononuclear Cells of HIV Exposed Seronegative Female Commercial Sex Workers from Nairobi Kenya. [Internet] [Thesis]. University of Manitoba; 2016. [cited 2019 Oct 22]. Available from: http://hdl.handle.net/1993/31141.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Omange RW. Toll-Like Receptor Responses in Peripheral Blood Mononuclear Cells of HIV Exposed Seronegative Female Commercial Sex Workers from Nairobi Kenya. [Thesis]. University of Manitoba; 2016. Available from: http://hdl.handle.net/1993/31141

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation


University of Manitoba

3. DRAGON, Stephane. Molecular Signaling Mechanisms and Effector Functions of the Interleukin-17 Receptor in Human Airway Smooth Muscle Cells and Polymorphonuclear Neutrophils.

Degree: Immunology, 2010, University of Manitoba

Immunopathological disorders are no longer defined by dysregulated T-helper (Th) type 1/ Th2 responses but account for modulatory cell types such as regulatory and Th17 cells. The newly defined Th17 subset is an effector memory subtype which regulates mucosal host defense responses. A distinctive feature of interleukin (IL)-17 is its ability to invoke neutrophilic responses and to synergize cytokine responses in proximal structural cells. This effect is most evident for proinflammatory cytokines and neutrophil-mobilizing chemokines which are under the regulatory control of the canonical, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. The uniqueness of the IL-17A receptor (IL-17RA) signal transduction pathway however has been a limiting factor in uncovering IL-17-mediated effector functions since the receptor bears little homology to other known receptors and contains a unique cytoplasmic consensus binding motif. Hence, the composition, dynamics and subunit interactions of the IL-17R complex have become an emerging area of research where novel recruitment motifs and adaptor proteins are actively being explored. Our study sought to uncover the signal transduction and molecular mechanisms mediating the initiation and amplification responses induced by IL-17. We hypothesize that (i) IL-17 represents a key cytokine which initiates inflammatory responses by acting on proximal structural cells to rapidly release neutrophil-mobilizing chemokines and myeloid growth factors and that (ii) IL-17 directly promotes survival responses of immune effector cells. Genomic analysis of stimulated human airway smooth muscle cells support the proinflammatory nature of IL-17 as NF-κB associated genes and chemokines were most significantly upregulated within 2 hours. However, IL-17 induced a modest fold increase in gene expression levels whereby only 4 genes achieved greater than 2 fold increases. This, along with the observation that IL-17 enhanced IL-1β-mediated CXCL8 expression via transcriptional promoter activation levels and post-transcriptional mRNA stabilization mechanisms suggests that IL-17 cooperatively functions with secondary cytokines to mediate inflammatory responses. Despite activating the p38-mitogen-activated protein kinase (MAPK) signaling pathway in peripheral blood neutrophils, IL-17 did not directly affect the apoptotic capacity of these cells but unexpectedly antagonized the survival response mediated by the granulocyte-macrophage colony stimulating factor (GM-CSF). Collectively, our results suggest that IL-17 is a potent synergistic cytokine which signals via the MAPK-NF-κB pathway to indirectly recruit neutrophils via CXC-chemokines produced by non-hematopoietic cells and that IL-17 may potentially dampen inflammatory responses by directly antagonizing inflammatory effector cells. Advisors/Committee Members: GOUNNI, Abdelilah SOUSSI (Immunology) (supervisor), MARSHALL, Aaron (Immunology) GIBSON, Spencer (Biochemistry and Medical Genetics) HALAYKO, Andrew (Physiology) KUMAR, Ashok (Pathology and Laboratory Medicine University of Ottawa) (examiningcommittee).

Subjects/Keywords: Human; Inflammation; Cytokines; IL-17; IL-1beta; IL-22; CXCL-8; airway smooth muscle cells; neutrophils; IL-17R; signal transduction; gene expression; apoptosis

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

DRAGON, S. (2010). Molecular Signaling Mechanisms and Effector Functions of the Interleukin-17 Receptor in Human Airway Smooth Muscle Cells and Polymorphonuclear Neutrophils. (Thesis). University of Manitoba. Retrieved from http://hdl.handle.net/1993/3945

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

DRAGON, Stephane. “Molecular Signaling Mechanisms and Effector Functions of the Interleukin-17 Receptor in Human Airway Smooth Muscle Cells and Polymorphonuclear Neutrophils.” 2010. Thesis, University of Manitoba. Accessed October 22, 2019. http://hdl.handle.net/1993/3945.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

DRAGON, Stephane. “Molecular Signaling Mechanisms and Effector Functions of the Interleukin-17 Receptor in Human Airway Smooth Muscle Cells and Polymorphonuclear Neutrophils.” 2010. Web. 22 Oct 2019.

Vancouver:

DRAGON S. Molecular Signaling Mechanisms and Effector Functions of the Interleukin-17 Receptor in Human Airway Smooth Muscle Cells and Polymorphonuclear Neutrophils. [Internet] [Thesis]. University of Manitoba; 2010. [cited 2019 Oct 22]. Available from: http://hdl.handle.net/1993/3945.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

DRAGON S. Molecular Signaling Mechanisms and Effector Functions of the Interleukin-17 Receptor in Human Airway Smooth Muscle Cells and Polymorphonuclear Neutrophils. [Thesis]. University of Manitoba; 2010. Available from: http://hdl.handle.net/1993/3945

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

.