Peripheral blood transcriptome and the characterization of chemical-structural and functional properties of immunoglobulin G in different clinical outcomes related to infection with Leishmania infantum chagasi

Abstract

Visceral leishmaniasis (VL), a disease that is endemic in Brazil, is fatal if not treated; however, the majority of human infections with the etiological agent Leishmania infantum chagasi, are asymptomatic. Several studies have contributed to the understanding of the response induced by infection during active disease in humans, nevertheless, there is still a lack of knowledge into molecular mechanisms that contribute to the pathogenesis or protection against the development of clinical symptoms upon infection and treatment. In view of these facts, we investigated the patterns of gene expression from whole blood; while characterized properties of immunoglobulin G, from VL patients, patients that received therapy, asymptomatic individuals and controls, that are affected at the post-translational level. Therefore, we demonstrated that the transcriptional profile of human whole blood, classified according to the clinical outcome related to the infection with L. infantum chagasi present significant differences; those differences reflect distinct characteristics in the enrichment of canonical biological pathways and blood transcriptional modules. The transcriptional profile of VL patients is associated to a low activity of pathways related to cellular migration and inflammation that may be important to parasite control. Those profiles change with treatment that is capable to revert the level of activity of those processes, besides of regulating responses associated to T and B lymphocytes. Importantly, our data point to the existence of a transcriptional network involved on the signaling by type I interferons, that might be important to responses associated to a resistance in the development of clinical symptoms. Furthermore, VL patients produce IgG with chemical-structural and functional profiles distinct from those observed for treated patients, asymptomatic individuals and controls. Those properties influence effector and regulatory functions of antibodies of IgG isotype, whereby the alterations observed in this study have the potential to influence VL immunopathology and raise new perspectives for the treatment of severe VL.