Regulation of immunity to cutaneous leishmaniasis by semaphorin 3E
| dc.contributor.author | Ikeogu, Nnamdi | |
| dc.contributor.examiningcommittee | Soussi Gounni, Abdelilah (Immunology) Murooka, Thomas (Immunology) Mckinnon, Lyle (Medical Microbiology and Infectious Diseases) | en_US |
| dc.contributor.supervisor | Uzonna, Jude (Immunology) | en_US |
| dc.date.accessioned | 2019-09-04T16:16:13Z | |
| dc.date.available | 2019-09-04T16:16:13Z | |
| dc.date.issued | 2019-08-28 | en_US |
| dc.date.submitted | 2019-08-28T20:43:02Z | en |
| dc.degree.discipline | Immunology | en_US |
| dc.degree.level | Master of Science (M.Sc.) | en_US |
| dc.description.abstract | Cutaneous Leishmaniasis is a disease of man and animals caused by the protozoan parasite Leishmania. Leishmania major is one of the major causative agents of cutaneous leishmaniasis. The host factors that regulate resistance to Leishmania major are not completely known but are influenced by the nature of innate and T helper cell responses. The limited understanding of the factors that influence resistance and susceptibility to the infection has delayed the development of vaccine and/or novel effective therapy against the disease. Semaphorin-3E (Sema3E), a mammalian membrane bound protein produced by several immune cells, has been reported to regulate cell migration and cell-mediated immune response, a critical arm of the immunity that controls resistance to intracellular pathogens such as Leishmania. However, the role played by Sema3E in immunity to cutaneous leishmaniasis has not been investigated before. To investigate the role of Sema3E in immunity to cutaneous leishmaniasis, I assessed the level of Sema3E expression in L. major-infected mice and observed a significant increase in Sema3E at different time points. Furthermore, Sema3E-deficient (Sema3E-/-) mice were more resistant to L. major infection than their WT counterparts as evidenced by significantly reduced lesion size and lower parasite burden, which was associated with significantly more IFN- and IL-17A production from CD4+ T cells in their draining lymph nodes than in WT mice. This was attributed to increased expression of costimulatory molecules and IL-12p40 by Sema3E-/- dendritic cells, increased frequency of Th1 and Th17 cells after polarization of Sema3E-/- CD4+ T cells, decreased frequency of T-regs and secreted IL-10 in the draining lymph node of Sema3E-/- mice compared to WT mice. Adoptive transfer of Sema3E-/- bone marrow cells to WT mice conferred better protection to the WT mice. Collectively, the results of my study show that the absence of Sema3E improves resistance to L. major infection in mice by enhancing stronger CD4+ Th1 and Th17 cell responses. These results indicate that Sema3E negatively regulates resistance to cutaneous leishmaniasis, suggesting that this pathway could be a potential drug target for controlling the disease. | en_US |
| dc.description.note | October 2019 | en_US |
| dc.identifier.uri | http://hdl.handle.net/1993/34150 | |
| dc.language.iso | eng | en_US |
| dc.rights | open access | en_US |
| dc.subject | Leishmania major | en_US |
| dc.subject | Semaphorin 3E | en_US |
| dc.subject | Cytokines | en_US |
| dc.subject | Immune response | en_US |
| dc.title | Regulation of immunity to cutaneous leishmaniasis by semaphorin 3E | en_US |
| dc.type | master thesis | en_US |