Open AccessTrypanosoma cruzi Needs a Signal Provided by Reactive Oxygen Species to Infect Macrophages
Author(s) -
Grazielle Ribeiro Goes,
Peter Rocha,
Aline R. S. Diniz,
Pedro Henrique Nascimento Aguiar,
Carlos Renato Machado,
Leda Quércia Vieira
Publication year - 2016
Publication title -
plos neglected tropical diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.99
H-Index - 135
eISSN - 1935-2735
pISSN - 1935-2727
DOI - 10.1371/journal.pntd.0004555
Subject(s) - trypanosoma cruzi , reactive oxygen species , oxidative stress , nadph oxidase , biology , respiratory burst , microbiology and biotechnology , macrophage , phagocytosis , immunology , parasite hosting , biochemistry , in vitro , world wide web , computer science
Background During Trypanosoma cruzi infection, macrophages produce reactive oxygen species (ROS) in a process called respiratory burst. Several works have aimed to elucidate the role of ROS during T . cruzi infection and the results obtained are sometimes contradictory. T . cruzi has a highly efficiently regulated antioxidant machinery to deal with the oxidative burst, but the parasite macromolecules, particularly DNA, may still suffer oxidative damage. Guanine (G) is the most vulnerable base and its oxidation results in formation of 8-oxoG, a cellular marker of oxidative stress. Methodology/Principal Findings In order to investigate the contribution of ROS in T . cruzi survival and infection, we utilized mice deficient in the gp91 phox (Phox KO) subunit of NADPH oxidase and parasites that overexpress the enzyme EcMutT (from Escherichia coli) or TcMTH (from T . cruzi ), which is responsible for removing 8-oxo-dGTP from the nucleotide pool. The modified parasites presented enhanced replication inside murine inflammatory macrophages from C57BL/6 WT mice when compared with control parasites. Interestingly, when Phox KO macrophages were infected with these parasites, we observed a decreased number of all parasites when compared with macrophages from C57BL/6 WT. Scavengers for ROS also decreased parasite growth in WT macrophages. In addition, treatment of macrophages or parasites with hydrogen peroxide increased parasite replication in Phox KO mice and in vivo . Conclusions Our results indicate a paradoxical role for ROS since modified parasites multiply better inside macrophages, but proliferation is significantly reduced when ROS is removed from the host cell. Our findings suggest that ROS can work like a signaling molecule, contributing to T . cruzi growth inside the cells.