Toxoplasma gondii infection positively modulates the macrophages migratory molecular complex by increasing matrix metalloproteinases, CD44 and alpha v beta 3 integrin.
Toxoplasmosis is a world wide spread zoonosis caused by Toxoplasma gondii, an obligate intracellular parasite that is able to disseminate into deep tissues and cross biological barriers, reaching immunoprivileged sites such as the brain and retina. The parasite is able to infect macrophages and dendritic cells for dispersal throughout the body. However, the molecular principals or outcomes of the subversion of the host cell are largely unknown. We evaluated the involvement of host invasive machinery in the migration of T. gondii infected murine cells from a monocytic/macrophage lineage. Migration in Matrigel of infected macrophages was augmented after 48 h of infection, and inhibition of metalloproteinases abolished migration. We also demonstrated that T. gondii infection induces a decreasing of CD44 at cell surface independent of the ERK signaling pathway, and that secretion of active MMP9 is augmented upon infection. Infected macrophages showed increased expression of MT1-MMP and ADAM10 membrane matrix metalloproteinases. Furthermore, processing of pro-alpha v and pro-beta 3 in T. gondii infected cells seems to depend on metalloproteinases to generate functional mature integrin alpha v beta 3 molecules, with no evidence of the involvement of proprotein convertase pathway.
Seipel
Daniele
D
Laboratório de Biologia do Reconhecer, Universidade Estadual do Norte Fluminense, Av. Alberto Lamego 2000, LBR 210/P4, Horto, Campos dos Goytacazes, Rio de Janeiro, CEP 28015-620, Brazil.
Oliveira
Bruno Cabral de Lima
BC
Resende
Thatiane Lacerda
TL
Schuindt
Sara Hellen Santos
SH
Pimentel
Pollyana M de Oliveira
PM
Kanashiro
Milton M
MM
Arnholdt
Andrea Cristina Vetö
AC
D051722:ADAM Proteins / Q000378:metabolism; D000072197:ADAM10 Protein; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D000818:Animals; D018960:Hyaluronan Receptors / Q000378:metabolism*; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000469:parasitology*; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D014122:Toxoplasma / Q000472:pathogenicity*
D018960:Hyaluronan Receptors; D039302:Integrin alphaVbeta3; D008565:Membrane Proteins; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D020782:Matrix Metalloproteinases; D053511:Matrix Metalloproteinase 14; D000072197:ADAM10 Protein; C491234:Adam10 protein, mouse