Name: RENAN GARCIA DE MOURA
Publication date: 23/08/2019
Advisor:
Name |
Role |
|---|---|
| DANIEL CLAUDIO DE OLIVEIRA GOMES | Advisor * |
Examining board:
| Name |
Role |
|---|---|
| FAUSTO EDMUNDO LIMA PEREIRA | Internal Examiner * |
Summary: Parasites from the Viannia subgenus that include Leishmania (Viannia) braziliensis are the
most wide spread species in the Americas, causing cutaneous leishmaniasis (CL). The
development of cutaneous lesions during CL is prevalent in more than 90% of cases and is
characterized by an intense local cell-mediated TH1 immune response, production of cytolytic
proteins and nitric oxide, which contribute to parasite control and tissue damage. In addition,
increased production of pro-inflammatory mediators such as TNF-α and IFN-γ are observed
systemically and locally in infected patients, playing an important role in the pathogenesis of
the disease. This exacerbated inflammatory state can induce the expression of inhibitory
receptors (IR), such as PD-1 and TIM-3, on the surface of T cells and their ligands on target
cells, in which its effects during CL is poorly understood. Also, chronic inflammation can
induce differentiation of memory T cells, which begin to express the surface markers such as
KLRG1 and CD57, to an extend that their replicative rate is impaired, which could affect the
diseases control. In this scenario, we evaluated the expression of this molecules in local T
cells, macrophages and neutrophils of patients with CL. Our results indicate that CL lesions
have accumulated CD4+ and CD8+ cells and also express PD-1, TIM-3, KLRG1 and CD57 at
a higher frequency than in normal skin. Furthermore, macrophages and neutrophils were
found to be present at a higher frequency in patients than in healthy controls, being also the
only group WHERE PD-L1 and PD-L2 ligands were expressed. Our work contribute to a better
understanting of IR and their role in the immunopathogenesis of CL, since their expression
weaken the development of an immunologic response, which could impair the local response
and contribute to parasite persistence.
