AUTHOR=Luz Yasmin , Rebouças Amanda , Bernardes Carla Polyana O. S. , Rossi Erik A. , Machado Taíse S. , Souza Bruno S. F. , Brodskyn Claudia Ida , Veras Patricia S. T. , dos Santos Washington L. C. , de Menezes Juliana P. B. 

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

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=11

YEAR=2023

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2023.1206049

DOI=10.3389/fcell.2023.1206049

ISSN=2296-634X

ABSTRACT=<p><bold>Background:</bold> Leishmaniasis results in a wide spectrum of clinical manifestations, ranging from skin lesions at the site of infection to disseminated lesions in internal organs, such as the spleen and liver. While the ability of <italic>Leishmania</italic>-infected host cells to migrate may be important to lesion distribution and parasite dissemination, the underlying mechanisms and the accompanying role of host cells remain poorly understood. Previously published work has shown that <italic>Leishmania</italic> infection inhibits macrophage migration in a 2-dimensional (2D) environment by altering actin dynamics and impairing the expression of proteins involved in plasma membrane-extracellular matrix interactions. Although it was shown that <italic>L. infantum</italic> induces the 2D migration of dendritic cells, <italic>in vivo</italic> cell migration primarily occurs in 3-dimensional (3D) environments. The present study aimed to investigate the migration of macrophages and dendritic cells infected by <italic>Leishmania</italic> using a 3-dimensional environment, as well as shed light on the mechanisms involved in this process.</p><p><bold>Methods:</bold> Following the infection of murine bone marrow-derived macrophages (BMDM), human macrophages and human dendritic cells by <italic>L. amazonensis</italic>, <italic>L. braziliensis</italic>, or <italic>L. infantum</italic>, cellular migration, the formation of adhesion complexes and actin polymerization were evaluated.</p><p><bold>Results:</bold> Our results indicate that <italic>Leishmania</italic> infection inhibited 3D migration in both BMDM and human macrophages. Reduced expression of proteins involved in adhesion complex formation and alterations in actin dynamics were also observed in <italic>Leishmania</italic>-infected macrophages. By contrast, increased human dendritic cell migration in a 3D environment was found to be associated with enhanced adhesion complex formation and increased actin dynamics.</p><p><bold>Conclusion:</bold> Taken together, our results show that <italic>Leishmania</italic> 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, suggesting a potential association between dendritic cells and disease visceralization.</p>