Name: RÉGIA FERREIRA MARTINS FERRER
Publication date: 20/09/2019
Advisor:
Name |
Role |
|---|---|
| DANIEL CLAUDIO DE OLIVEIRA GOMES | Advisor * |
Examining board:
| Name |
Role |
|---|---|
| DANIEL CLAUDIO DE OLIVEIRA GOMES | Advisor * |
| RICARDO PINTO SCHUENCK | Internal Examiner * |
| RODRIGO RIBEIRO RODRIGUES | Internal Examiner * |
| SANDRA LÚCIA VENTORIN VON ZEIDLER | External Examiner * |
Summary: Leishmaniasis is a chronic disease with different clinical forms, which depend on the parasite species and the host's immune response. Localized Cutaneous Leishamnasis (LCL) is the most common form found in the world. Due to the importance of T-cell-mediated immune response in controlling L. braziliensis infection and in the immunopathogenesis of LCL, the aim of our study was to characterize senescence in memory T-cells, assess their secretory profile and activity and their role in the immunopathogenesis of LCL. For instance, our results showed that T-lymphocytes from patients with LCL have characteristics of senescent cells with increased expression of extracellular receptors such as KLRG-1 and CD57; as well as activation of protein kinase p38 intracellular signaling pathway, histone γH2AX; followed by telomere shortening and low expression of hTERT enzyme. Our research also demonstrated in the LCL group, an accumulation of terminally differentiated effector memory T (TEMRA) cells with senescence characteristics. We also found that, although these cells have proliferative defects, they have developed the Senescence-Associated Secretory Phenotype (SASP) phenotype, with high effector potential for the production of proinflammatory cytokines, e.g. TNF-α and IFN-γ. Besides that, we observed that patients' senescent cells have increased expression of CLA, associated with the ability to migrate to skin tissue, which was positively correlated with the senescent cells accumulation and the skin lesion size. In conclusion, we showed at first time the development of senescence over the T cells in patients with LCL, whose inflammatory and migratory potential may be associated with disease immunopathogenesis. These findings may contribute to the development of immunotherapy-based treatments, such as blockade of cell receptors and/or signaling pathways, which would be able to enable the recovery of cell proliferative capacity and regulation of proinflammatory cytokines, as well as emerging new biomarkers that may be associated with the disease severity
