Enhanced Migratory Capacity of T Lymphocytes in Severe Chagasic Patients Is Correlated With VLA-4 and TNF-α Expression

BERBERT L; GONZALEZ F; VILLAR, SILVINA; VIGLIANO C; LIOI S; BELOSCAR J; BOTTASSO O; SILVA-BARBOSA SD; SAVINO W; PEREZ A

Frontiers in cellular and infection microbiology

Frontiers Media

Lugar: Louisville; Año: 2021 vol. 11 p. 1 - 11

2235-2988

Trypanosoma cruzi infection in humans leads to progression to chronic chagasicmyocarditis (CCM) in 30% of infected individuals, paralleling T cell inflammatoryinfiltrates in the heart tissue. T-cell trafficking into the hearts of CCM patients may bemodulated by in situ expression of chemotactic or haptotactic molecules, as thechemokine CXCL12, the cytokine tumor necrosis factor-alpha (TNF-a), and extracellularmatrix proteins (ECM), such as fibronectin. Herein we evaluated the expression offibronectin, CXCL12, and TNF-a in the myocardial tissue of T. cruzi seropositive(asymptomatic or with CCM), as well as seronegative individuals as healthy controls.Hearts from CCM patients exhibited enhanced expression of these three molecules.CXCL12 and TNF-a serum levels were also increased in CCM individuals. We thenevaluated T lymphocytes from chronic chagasic patients by cytofluorometry, in terms ofmembrane expression levels of molecules involved in cell activation and cell migration,respectively, HLA-DR and the VLA-4 (very late antigen-4, being one integrin-typefibronectin receptor). Indeed, the expression of HLA-DR and VLA-4 was enhanced onT lymphocytes from chagasic patients, especially in the CCM group. To further approachthe dynamics of T cell migratory events, we performed fibronectin-, TNF-a-, and CXCL12-driven migration. Peripheral blood mononuclear cells (PBMCs) and T cells from CCMpatients presented an ex vivo enhanced migratory capacity driven by fibronectin alonewhen this ECM protein was placed in the membrane of transwell migration chambers.When TNF-a was previously placed upon fibronectin, we observed a further andsignificant increase in the migratory response of both PBMCs and T lymphocytes.Overall, these data suggest the existence in patients with chronic Chagas disease of acardiac inflammatory infiltrate vector that promotes the recruitment and accumulation ofactivated T cells, driven in part by enhanced tissue expression of fibronectin and TNF-a,as well as the respective corresponding VLA-4 and TNF receptors.