Estudo do papel do lpg2 na migração de células dendríticas infectadas por Leishmania infantum

INTRODUCTION: Leishmaniasis is a zoonosis caused by protozoa of the genus Leishmania, which can manifest in different clinical forms. The dissemination and homing of infected cells containing Leishmania antigens are critical for the parasite's survival in the host and for lesion establishment. In addition to host factors, intrinsic factors of the parasite are important for maintaining infection in the host. Recent studies highlight the importance of Leishmania lipophosphoglycan (LPG) in the interaction with host cells, the parasite's survival mechanisms, and the establishment of infection. However, the relationship between LPG and dendritic cell migration remains to be elucidated, considering that these cells are responsible for capturing, processing, and presenting antigens, as well as regulating the migration of immune cells to infection sites. Their interaction with the Leishmania parasite is crucial for the visceralization of infection and disease control. OBJECTIVE: Thus, this study aims to evaluate the role of lpg2 in the migration of human host cells infected by L. infantum. METHODS: Human dendritic cells were cultured, infected with wild-type L. infantum, Δlpg2, or Δlpg2 + lpg2, and subjected to migration in a Transwell system. Additionally, immunostaining was performed with antibodies against pFAK and pPaxillin to evaluate adhesion complex formation; Talin and Vinculin to assess podosome formation; and Rac1, Cdc42, Gelsolin, RhoA, and phalloidin to evaluate actin polymerization using confocal microscopy. Furthermore, the expression of CCR7 in dendritic cells infected by different Leishmania strains was assessed by flow cytometry. Finally, to investigate the activation of the ERK1/2 signaling pathway, we evaluated the expression of ERK1/2 protein using the western blot technique. RESULTS: The results demonstrate a reduction in dendritic cell migration following infection with L. infantum Δlpg2 compared to cells infected with the wild-type or Δlpg2 + lpg2, which is associated with reduced adhesion complex formation, podosome formation, and actin dynamics. Additionally, lower CCR7 and ERK1/2 expression was observed in dendritic cells infected by L. infantum Δlpg2 compared to cells infected with the wild-type or Δlpg2 + lpg2. CONCLUSIONS: The data presented in this study suggest that L. infantum LPG positively modulates the migration of human dendritic cells by enhancing adhesion complex formation, podosome formation, and actin dynamics in these cells, as well as increasing CCR7 expression and ERK1/2 pathway activation. Additional experiments are needed to better understand the role of LPG in modulating these cells infected by L. infantum.

Grantor dc:publisher

Universidade Federal da Bahia

Year dc:date.issued

2024

Author dc:creator

• Bernardes, Carla Polyana Oliveira Silva

• Células dendríticas
• Migração
• Leishmania
• Lipofosfoglicano
• LPG

Statement dc:rights

• Acesso Aberto

Language dc:language

por

Repository record dc:identifier.uri

https://repositorio.ufba.br/handle/ri/42693

OAI identifier oai:identifier

oai:repositorio.ufba.br:ri/42693