Banca de DEFESA: Elane Priscila Maciel

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : Elane Priscila Maciel
DATE: 22/09/2023
TIME: 14:00
LOCAL: Plataforma Teams
TITLE:

Inhibitory pathways in human immune response to Leishmania spp

KEY WORDS:

Leishmania, dendritic cells, PD1-PDL-1 

PAGES: 55
BIG AREA: Ciências da Saúde
AREA: Medicina
SUMMARY:

INTRODUCTION Leishmania braziliensis causes a proinflammatory disease, with localized lesions and a possible mucosal commitment. On the other hand, Leishmania infantum is involved in the visceral form, with a specific cellular response anergy. Previous data from our group showed that DC-SIGN expression in moDCs (monocytes derived Dendritic Cells) was decreased after L. braziliensis and L. infantum infection, probably compromising DC function and T cell activation, as a parasite scape mechanism. Besides that, parasites can induce inhibitory molecules that also could be involved in T cell anergy. METHODS This research focused the PD1-PDL1 pathway in human moDCs infected with L. braziliensis or L. infantum, studying cell surface molecules expression as well as antibodies to block PD1-PDL1 pathway. This study was approved by the faculty ethics commission (CEP/FM/UnB - CAAE 33062720.6.0000.5558). RESULTS Infection rate measured with optical microscopy was 76% (±8.83) for L. infantum, while for L. braziliensis it was 50% (±10.97). When determined by flow cytometry, infection rate was 69.05% (±4.56) for L. infantum and 35.25% (±5.56) for L. braziliensis. Was observed a down modulation of DC-SIGN on DCs bystanders (non-infected cells from the same well where Leishmania was added) for L. infantum (64,95% ±9,36) and L. braziliensis (72,4% ±1,71), compared to control DCs (84,70% ±5,07). We also observed an increase on PDL1 in DCs infected with L. braziliensis (99,55% ±19,06) or bystanders (86,85% ±22,24) as well as for DC infected with L. infantum (99,6% ±0,41) or bystander DCs (86,40% ±7,96). By blocking cell co-culture with anti-PDL1, IFN-g production from CD4 cells, raised from 1,94 (±0,91) in L. braziliensis infected DCs to 8,16% (±4,33) when anti-PD-1 was used. The same effect was observed for L. infantum with an increase from 1,79 % (±1,18) to 5,38 (±3,69) when PD1-PDL1 pathway was blocked. For CD8 T cells IFN-g raised from 7,38 (±2,34) in L. braziliensis infection to 21,40 (±7,47) by blocking PD1-PDL1. The same effect was also observed for L. infantum infection, with 5,97 (±1,66) CD8+IFN+ cells and upregulating to 14 (±4,53) by blocking PD1-PDL1. CONCLUSIONS L. braziliensis and L. infantum infection, or their soluble products, increased the expression of PD1 on moDCs, probably impairing T cell IFN-g production that could control parasites spread.

 

 

COMMITTEE MEMBERS:
Presidente - 1466693 - CECILIA BEATRIZ FIUZA FAVALI
Interno - 1876284 - VICENTE DE PAULO MARTINS
Externa à Instituição - CLARISSA ROMERO TEIXEIRA - FIOCRUZ
Externa à Instituição - NATALIA MACHADO TAVARES - FIOCRUZ
Externa à Instituição - SHÉLIDA VASCONCELOS BRAZ - UFMA