Research Article: Differential Activation of Human Monocytes and Lymphocytes by Distinct Strains of Trypanosoma cruzi

Date Published: July 6, 2015

Publisher: Public Library of Science

Author(s): Luísa M. D. Magalhães, Agostinho Viana, Egler Chiari, Lúcia M. C. Galvão, Kenneth J. Gollob, Walderez O. Dutra, Eric Dumonteil.

Abstract: BackgroundTrypanosoma cruzi strains are currently classified into six discrete typing units (DTUs) named TcI to VI. It is known that these DTUs have different geographical distribution, as well as biological features. TcI and TcII are major DTUs found in patients from northern and southern Latin America, respectively. Our hypothesis is that upon infection of human peripheral blood cells, Y strain (Tc II) and Col cl1.7 (Tc I), cause distinct immunological changes, which might influence the clinical course of Chagas disease.Methodology/Principal FindingsWe evaluated the infectivity of CFSE-stained trypomastigotes of Col cl1.7 and Y strain in human monocytes for 15 and 72 hours, and determined the immunological profile of lymphocytes and monocytes exposed to the different isolates using multiparameter flow cytometry. Our results showed a similar percentage and intensity of monocyte infection by Y and Col cl1.7. We also observed an increased expression of CD80 and CD86 by monocytes infected with Col cl1.7, but not Y strain. IL-10 was significantly higher in monocytes infected with Col cl1.7, as compared to Y strain. Moreover, infection with Col cl1.7, but not Y strain, led to an increased expression of IL-17 by CD8+ T cells. On the other hand, we observed a positive correlation between the expression of TNF-alpha and granzyme A only after infection with Y strain.Conclusion/SignificanceOur study shows that while Col cl1.7 induces higher monocyte activation and, at the same time, production of IL-10, infection with Y strain leads to a lower monocyte activation but higher inflammatory profile. These results show that TcI and TcII have a distinct immunological impact on human cells during early infection, which might influence disease progression.

Partial Text: Human infection with the protozoan parasite, Trypanosoma cruzi, leads to Chagas disease, which presents as a spectrum of clinical forms, ranging from a relatively mild form (indeterminate), to a severe heart disease that affects approximately 30% of the infected individuals. Chagas disease is endemic to Latin America and the pathogenesis of Chagas heart disease is not clearly understood. A combination of host genetics, the host immune response and parasite factors seem to play important roles in the process [1] [2].

A triad of factors involving host genetics, immune competence of the affected population, and genetic diversity of the parasite influence the outcome of Chagas disease [1]. Our goal was to evaluate the effects of infection with either the Y (Tc II) or Col cl1.7 (Tc I) strains on immunological characteristics of human peripheral blood cells. These two strains were isolated from humans and represent the two major genetic groups of T. cruzi–Tc I (Col cl1.7) and Tc II (Y strain) [10] [19].



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