Dados do Trabalho

Título

Leishmania infection alters macrophage and dendritic cell migration in a three-dimensional environment

Introdução

Leishmaniasis gives rise to a diverse spectrum of clinical manifestations, encompassing cutaneous lesions at the infection site to disseminated lesions in internal organs, such as the liver and spleen. The migratory behavior of Leishmania-infected host cells assumes significant importance in lesion distribution and parasite dissemination. Nevertheless, the underlying mechanisms governing this migration and the precise involvement of host cells remain inadequately understood. Previously published work has shown that Leishmania infection impedes macrophage migration in a two-dimensional (2D) milieu through perturbations in actin dynamics and impairment of proteins engaged in cell membrane-extracellular matrix interactions. While it has been elucidated that L. infantum induces 2D migration of dendritic cells, in vivo cellular migration primarily transpires within three-dimensional (3D) environments.

Objetivo (s)

The present study aimed to investigate the migration of macrophages and dendritic cells infected by Leishmania using a 3D environment, as well as shed light on the mechanisms involved in this process.

Material e Métodos

Bone marrow-derived macrophages (BMDM), human macrophages, and human dendritic cells were infected with L. amazonensis, L. braziliensis, or L. infantum. Cellular migration was evaluated using the transwell system or a high-content analysis system. The mechanisms of migration were analyzed through immunofluorescence, using anti-pFak and anti-pPaxillin antibodies for adhesion complex formation, and anti-RhoA, anti-Cdc42, anti-Rac1, and phalloidin for actin polymerization.

Resultados e Conclusão

Leishmania infection exerts an inhibitory effect on the 3D migration of BMDM and human macrophages, associated with a reduction in the expression of proteins involved in the formation of adhesion complexes and actin cytoskeleton dynamics. On the other hand, we observed a remarkable increase in the 3D migratory capacity of human dendritic cells, accompanied by enhanced formation of adhesion complexes and actin cytoskeleton dynamics.Taken together, our results show that Leishmania infection inhibits macrophage 3D migration, while enhancing dendritic 3D migration by altering actin dynamics and the expression of proteins involved in plasma membrane extracellular matrix interactions.

Palavras-chave

Macrophages, Dendritic cells, 3D Migration, Leishmania

Agradecimentos

This study was funded by grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Programa Inova Fiocruz.