title: Leishmania infection inhibits macrophage motility by altering F-actin dynamics and the expression of adhesion complex proteins.
abstract: Leishmania is an intracellular protozoan parasite that causes a broad spectrum of clinical manifestations, ranging from self-healing skin lesions to fatal visceralizing disease. As the host cells of choice for all species of Leishmania, macrophages are critical for the establishment of infections. How macrophages contribute to parasite homing to specific tissues and how parasites modulate macrophage function are still poorly understood. In this study, we show that Leishmania amazonensis infection inhibits macrophage roaming motility. The reduction in macrophage speed is not dependent on particle load or on factors released by infected macrophages. L. amazonensis-infected macrophages also show reduced directional migration in response to the chemokine MCP-1. We found that infected macrophages have lower levels of total paxillin, phosphorylated paxillin, and phosphorylated focal adhesion kinase when compared to noninfected macrophages, indicating abnormalities in the formation of signaling adhesion complexes that regulate motility. Analysis of the dynamics of actin polymerization at peripheral sites also revealed a markedly enhanced F-actin turnover frequency in L. amazonensis-infected macrophages. Thus, Leishmania infection inhibits macrophage motility by altering actin dynamics and impairing the expression of proteins that function in plasma membrane-extracellular matrix interactions.
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, Maryland, USA.|Laboratório de Patologia e Biointervenção, CPqGM, FIOCRUZ, Salvador, Bahia, Brazil.
authors.forename: Juliana Perrone Bezerra
authors.initials: JP
authors.lastname: de Menezes
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, Maryland, USA.
authors.forename: Amrita
authors.initials: A
authors.lastname: Koushik
authors.affiliation: Department of Physics, University of Maryland, Maryland, USA.
authors.forename: Satarupa
authors.initials: S
authors.lastname: Das
authors.affiliation: Department of Physics, University of Maryland, Maryland, USA.
authors.forename: Can
authors.initials: C
authors.lastname: Guven
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, Maryland, USA.
authors.forename: Ariel
authors.initials: A
authors.lastname: Siegel
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, Maryland, USA.
authors.forename: Maria Fernanda
authors.initials: MF
authors.lastname: Laranjeira-Silva
authors.affiliation: Department of Physics, University of Maryland, Maryland, USA.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Losert
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, Maryland, USA.
authors.forename: Norma W
authors.initials: NW
authors.lastname: Andrews
mesh_terms: D000199:Actins / Q000378:metabolism*; D002465:Cell Movement; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000032:analysis; D007894:Leishmania mexicana / Q000472:pathogenicity*; D008264:Macrophages / Q000737:chemistry / Q000469:parasitology* / Q000502:physiology*; D051419:Paxillin / Q000032:analysis
chemical_list: D000199:Actins; D051419:Paxillin; D051416:Focal Adhesion Protein-Tyrosine Kinases