ANALYSIS OF THE INFLAMMATORY PROFILE AND PHENOTYPIC CHARACTERIZATION OF SENESCENT AND MEMORY RESIDENT CELLS IN HUMAN CUTANEOUS LEISHMANIASIS CAUSED BY Leishmania braziliensis
Name: RENAN GARCIA DE MOURA
Publication date: 15/03/2024
Examining board:
Name |
Role |
|---|---|
| CARLOS GRAEFF TEIXEIRA | Examinador Interno |
| CELIO GERALDO FREIRE DE LIMA | Examinador Externo |
| DÉBORA DECOTE RICARDO DE LIMA | Examinador Externo |
| FAUSTO EDMUNDO LIMA PEREIRA | Examinador Interno |
Summary: Localized cutaneous leishmaniasis is a disease caused by parasites of the Leishmania genus, which develops from an exacerbated host immune response to the infection. In recent years, the disease has been associated with the early induction of a senescence profile in cells of the immune system (lymphocytes), making them highly cytotoxic and developing a state of systemic inflammation. However, little is known about the presence and phenotype of senescent cells in leishmaniasis lesions, which was the motivation for the development of this work. In this sense, it was observed, by flow cytometry and immunofluorescence, that populations of CD4+ and CD8+ T cells accumulate in the lesions and display different memory profiles from cells in circulation, with accumulation of more differentiated subsets. Similarly to what is already known systemically, it was demonstrated that the lesional environment is rich in pro-inflammatory cytokines, such as IL-1, IL-6, IL-8, IFN-, and TNF-, which are known to induce cells into senescence. Indeed, it was found that, compared to healthy skin, the lesions have an accumulation of T lymphocytes (CD4+ and CD8+), fibroblasts, and macrophages expressing the main markers of senescence: differentiation receptors (CD57 and KLRG1), DNA damage markers (yH2Ax), cell cycle inhibitors (p16), and those present in cellular stress pathways (ATF2), as well as molecules associated with antigen-independent effector functions (NKG2 family receptors and their ligands, HLA-E and MIC-A/B). Furthermore, it was found that, although most lesional lymphocytes originate from circulation, there are populations of differentiated cells that permanently reside in the skin, identified by the expression of CD69, CD103, and CD49a molecules. Collectively, these data indicate that T cells with senescence and residence phenotypes accumulate in the lesions, which could be associated with disease progression, as both populations are known for their highly cytotoxic effector activities, making them a potential target for future immunotherapies.
