Circulating T Follicular Helper Cell Abnormalities Associated to Different Clinical Forms of Chronic Chagas Disease

HERNÁNDEZ-VÁSQUEZ, YOLANDA; QUEBRADA PALACIO, LUZ P.; PETRAY, PATRICIA B.; QUEBRADA PALACIO, LUZ P.; PETRAY, PATRICIA B.; FERNÁNDEZ, ESTEBAN R.; POSTAN, MIRIAM; FERNÁNDEZ, ESTEBAN R.; POSTAN, MIRIAM; HERNÁNDEZ-VÁSQUEZ, YOLANDA

Frontiers in Cellular and Infection Microbiology

Frontiers

Lugar: Seattle; Año: 2020 vol. 10 p. 1 - 10

2235-2988

Multiple perturbations of the immune response affecting a range of cells havebeen reported in Trypanosoma cruzi-infected individuals and associated to clinicalmanifestations of chronic Chagas disease. There is a paucity of knowledge about therole of T follicular helper (Tfh) cells in this infection. Here, we sought to characterizecirculating Tfh (cTfh) cells in chronic Chagas disease patients and to identify potentialassociations with disease severity in humans. cTfh cells were characterized byflow cytometry in freshly isolated PBMCs from 7 T. cruzi-infected asymptomaticpatients (ASYMP), 5 patients with chronic chagasic dilated cardiomyopathy(CCC) and 8 healthy controls, using antibodies against chemokine receptorsCXCR5, CXCR3, CCR6, and CCR7. Our results showed significant expansion ofCD4+CD45RO+CXCR5+CCR6+ cells in ASYMP and CCC patients, along witha contraction of CD4+CD45RO+CXCR5+CXCR3-CCR6- (cTfh2) cells. ASYMPpatients further exhibited decreased CD4+CD45RO+CXCR5+CXCR3+CCR6- (cTfh1)cells and expanded CD4+CD45RO+CXCR5+CXCR3-CCR6+ (cTfh17)cells while CCC patients exhibited significantly increased frequencies ofCD4+CD45RO+CXCR5+CCR7+ cells. Linear regression analysis revealed a positivetrend of CD4+CD45RO+CXCR5+CXCR3+CCR6+ (cTfh1/17) cells and negativetrends of cTfh1 and cTfh2 cells as disease was more severe. There was no correlationbetween the frequencies of cTfh cells and circulating CD19+IgD-IgG+ cells or serumlevels of T. cruzi-specific IgG. These results demonstrate that the cTfh compartmentof humans chronically infected with T. cruzi comprises expanded CCR6-expressingcells and reduced cTfh2 cells. The association of discrete phenotypic changes in cTfhsubsets with different clinical forms suggests the potential contribution of T follicularhelper cells to Chagas heart disease progression.