title: Altered thymocyte migration during experimental acute Trypanosoma cruzi infection: combined role of fibronectin and the chemokines CXCL12 and CCL4.
abstract: We previously showed migration disturbances in the thymus during experimental infection with Trypanosoma cruzi, the causative agent of Chagas disease. These changes were related to the enhanced expression of extracellular matrix ligands and receptors, leading to the escape of immature cells to the periphery. Here, we analyzed the expression and role of selected chemokines (CXCL12 and CCL4) and their receptors (CXCR4 and CCR5) in regulating thymocyte migration in conjunction with extracellular matrix during acute T. cruzi infection. We found increased chemokine deposition in the thymus of infected mice when compared to controls, accompanied by enhanced co-localization with fibronectin as well as up-regulated surface expression of CXCR4 and CCR5 in thymocytes. We also noticed altered thymocyte migration towards the chemokines analyzed. Such an enhancement was even more prominent when fibronectin was added as a haptotatic stimulus in combination with a given chemokine. Our findings suggest that thymocyte migration results from a combined action of chemokines and extracellular matrix (ECM), which can be altered during pathological conditions such as T. cruzi infection, and may be at the origin of the changes in the T cell repertoire seen in this pathological process.
authors.affiliation: Laboratory of Thymus Research, Department of Immunology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Daniella Arêas
authors.initials: DA
authors.lastname: Mendes-da-Cruz
authors.forename: João Santana
authors.initials: JS
authors.lastname: Silva
authors.forename: Vinícius
authors.initials: V
authors.lastname: Cotta-de-Almeida
authors.forename: Wilson
authors.initials: W
authors.lastname: Savino
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000276:immunology*; D014355:Chagas Disease / Q000276:immunology* / Q000469:parasitology; D054407:Chemokine CCL4; D054377:Chemokine CXCL12; D019742:Chemokines, CC / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D005109:Extracellular Matrix / Q000276:immunology / Q000469:parasitology; D005353:Fibronectins / Q000276:immunology*; D007150:Immunohistochemistry; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D019713:Receptors, CCR5 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000469:parasitology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000469:parasitology; D014349:Trypanosoma cruzi / Q000276:immunology*
chemical_list: C496535:Ccl4 protein, mouse; D054407:Chemokine CCL4; D054377:Chemokine CXCL12; D019742:Chemokines, CC; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D005353:Fibronectins; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D019713:Receptors, CCR5; D019718:Receptors, CXCR4