The in vitro interaction of Sporothrix schenckii with human endothelial cells is modulated by cytokines and involves endothelial surface molecules.
Sporothrix schenckii is the etiological agent of sporotrichosis, a subcutaneous mycosis that can evolve to systemic complications in immunocompromised patients. Interactions with endothelium are thought to be essential for systemic infections. In the present work, we studied the interaction between S. schenckii and human umbilical vein endothelial cells (HUVECs). S. schenckii interacts with HUVECs in a time-dependent manner. Morphological analysis showed that yeasts locate to interendothelial junctions. Ultrastructural studies showed that internalized yeasts were found inside endocytic vacuoles as early as 2 h, without causing any detectable damage to HUVECs after 24 h of infection. The viability of infected HUVECs was confirmed by the MTT assay. When HUVECs were treated with different concentrations of Interleukin-1beta or transforming growth factor-beta, a significant dose-dependent increase in cell-associated yeasts was observed. The preliminary analysis of the endothelial surface ligands for S. schenckii cells revealed two major molecules, with Mr of approximately 90 and 135 kDa. The interaction of endothelial cell surface molecules with S. schenckii yeast cells was modulated by divalent cations. This is the first demonstration that S. schenckii is able to adhere and invade endothelial cells without significantly affect cellular integrity. Our results suggest the contribution of cytokine-modulated calcium-dependent molecules to this process.
Departamento de Biologia Celular e Genética, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro (UERJ), Rua Sao Francisco Xavier, 524, PHLC sala 205, Maracana, Rio De Janeiro, RJ, 20550-013, Brazil. Veronica@uerj.br
Camila Castro
CC
Figueiredo
Osana Cunha
OC
De Lima
Laís
L
De Carvalho
Leila Maria
LM
Lopes-Bezerra
Verônica
V
Morandi
D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000302:isolation & purification / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology / Q000502:physiology*; D042783:Endothelial Cells / Q000737:chemistry* / Q000187:drug effects / Q000382:microbiology* / Q000648:ultrastructure; D005562:Formazans / Q000378:metabolism; D006801:Humans; D007365:Intercellular Junctions / Q000382:microbiology; D007375:Interleukin-1 / Q000494:pharmacology / Q000502:physiology; D008565:Membrane Proteins / Q000302:isolation & purification / Q000378:metabolism; D011485:Protein Binding; D013175:Sporothrix / Q000472:pathogenicity* / Q000502:physiology; D013778:Tetrazolium Salts / Q000378:metabolism; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000502:physiology; D022161:Transport Vesicles / Q000382:microbiology
D015815:Cell Adhesion Molecules; D016207:Cytokines; D005562:Formazans; D007375:Interleukin-1; D008565:Membrane Proteins; D013778:Tetrazolium Salts; D016212:Transforming Growth Factor beta; C079782:MTT formazan; D002118:Calcium