Trypanosoma cruzi Mexican Strains Differentially Modulate Surface Markers and Cytokine Production in Bone Marrow-Derived Dendritic Cells from C57BL/6 and BALB/c Mice.

Cecilia Gomes Barbosa,Malú Mateus Santos,Virmondes Rodrigues,Luiz Eduardo Ramirez,Tamires Marielem Carvalho Costa,César Gómez Hernández,Weslley Guimarães Bovi,Mariana De Oliveira Silva,Paula Tatiana Mutão Ferreira,Rafael Obata Trevisan,Carlo José Freire De Oliveira,Marcos Vinícius Da Silva,Juliana Reis Machado,Chamberttan Souza Desidério

doi:10.1155/2019/7214798

Cecilia Gomes Barbosa, Malú Mateus Santos + Show 12 more

Open Access

https://doi.org/10.1155/2019/7214798

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Abstract

Dendritic cells (DCs) are a type of antigen-presenting cells that play an important role in the immune response against Trypanosoma cruzi, the causative agent of Chagas disease. In vitro and in vivo studies have shown that the modulation of these cells by this parasite can directly affect the innate and acquired immune response of the host in order to facilitate its biological cycle and the spreading of the species. Many studies show the mechanisms by which T. cruzi modulates DCs, but the interaction of these cells with the Mexican strains of T. cruzi such as Ninoa and INC5 has not yet been properly investigated. Here, we evaluated whether Ninoa and INC5 strains evaded the immunity of their hosts by modulating the biology and function of murine DCs. The CL-Brener strain was used as the reference strain. Herein, it was demonstrated that Ninoa was more infective toward bone marrow-derived dendritic cells (BMDCs) than INC5 and CL-Brener strains in both BMDCs of BALB/c and C57BL/6 mice. Mexican strains of T. cruzi induced different cytokine patterns. In BMDCs obtained from BALB/c mice, Ninoa strain led to the reduction in IL-6 and increased IL-10 production, while in C57BL/6 mice Ninoa strain considerably increased the productions of TNF-α and IL-10. Also, Ninoa and INC5 differentially modulated BMDC expressions of MHC-II, TLR2, and TLR4 in both BALB/c and C57BL/6 mice compared to Brazilian strain CL-Brener. These results indicate that T. cruzi Mexican strains differentially infect and modulate MHC-II, toll-like receptors, and cytokine production in DCs obtained from C57BL/6 and BALB/c mice, suggesting that these strains have developed particular modulatory strategies to disrupt DCs and, consequently, the host immune responses.

Highlights

Chagas disease, an illness identified 110 years ago by the physician and researcher Carlos Chagas, is a serious public health problem, affecting approximately 8 million people worldwide [1, 2]
In bone marrow-derived dendritic cells (BMDCs) derived from BALB/c mice, the percentage of cells infected with the different strains did not show a significant difference despite experiencing a slight increase when these cells were cultured with LPS (Figure 1(a))
When evaluating the amount of parasites present in a total of 100 BMDCs, we found that cells cultured with T. cruzi from the Ninoa strain previously stimulated with LPS exhibited a significant increase in the number of parasites compared to the INC5 strain plus LPS (p = 0 0427) (Figure 1(b))

Summary

Introduction

An illness identified 110 years ago by the physician and researcher Carlos Chagas, is a serious public health problem, affecting approximately 8 million people worldwide [1, 2]. The strains belonging to the same TcI genotype differ in their ability to invade cells and cause infection [16,17,18,19,20,21]. Experimental studies have shown that the Mexican strains belong to the same TcI genotype, they present differences in the induction of mortality (0–100%), muscle cell tropism (mainly skeletal and cardiac), and in the inflammatory process generated by the infection. This indicates that biological behavior varies between these strains in the same DTU [16, 17, 19, 20].

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