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

• Grant number: 11/23819-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): April 01, 2012
• Effective date (End): January 31, 2015
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Isabel Kinney Ferreira de Miranda Santos
• Grantee: Luiz Gustavo Araujo Gardinassi
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

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.

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

GARDINASSI, LUIZ GUSTAVO; GARCIA, GUSTAVO ROCHA; NERY COSTA, CARLOS HENRIQUE; SILVA, VLADIMIR COSTA; FERREIRA DE MIRANDA SANTOS, ISABEL KINNEY. Blood Transcriptional Profiling Reveals Immunological Signatures of Distinct States of Infection of Humans with Leishmania infantum. PLoS Neglected Tropical Diseases, v. 10, n. 11, NOV 2016. (13/00382-0, 11/23819-0, 14/25856-8, 12/06708-2)

GARDINASSI, LUIZ GUSTAVO; DOTZ, VIKTORIA; EDERVEEN, AGNES HIPGRAVE; DE ALMEIDA, ROQUE PACHECO; NERY COSTA, CARLOS HENRIQUE; COSTA, DORCAS LAMOUNIER; DE JESUS, AMELIA RIBEIRO; MAYBORODA, OLEG A.; GARCIA, GUSTAVO ROCHA; WUHRER, MANFRED; et al. Clinical Severity of Visceral Leishmaniasis Is Associated with Changes in Immunoglobulin G Fc N-Glycosylation. MBIO, v. 5, n. 6, NOV-DEC 2014. (13/00382-0, 12/06708-2, 11/23819-0)

GARCIA, GUSTAVO ROCHA; GARDINASSI, LUIZ GUSTAVO; RIBEIRO, JOSE MARCOS; ANATRIELLO, ELEN; FERREIRA, BEATRIZ ROSSETTI; SANTANNA MOREIRA, HIGO NASSER; MAFRA, CLAUDIO; MARTINS, MARIA MARLENE; JUAN SZABO, MATIAS PABLO; FERREIRA DE MIRANDA-SANTOS, ISABEL KINNEY; et al. The sialotranscriptome of Amblyomma triste, Amblyomma parvum and Amblyomma cajennense ticks, uncovered by 454-based RNA-seq. PARASITES & VECTORS, v. 7, SEP 8 2014. (11/23819-0)

GARDINASSI, LUIZ GUSTAVO; DESOUZA-VIEIRA, THIAGO S.; DA SILVA, NAILA O.; GARCIA, GUSTAVO R.; BORGES, VALERIA M.; CAMPOS, ROSEANE N. S.; DE ALMEIDA, ROQUE P.; DE MIRANDA SANTOS, ISABEL K. F.; SARAIVA, ELVIRA M.. Molecular signatures of neutrophil extracellular traps in human visceral leishmaniasis. PARASITES & VECTORS, v. 10, JUN 6 2017. (14/25856-8, 13/00382-0, 11/23819-0)