Molecular signatures of neutrophil extracellular traps in human visceral leishmaniasis

Author(s)

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.

• Document type: Journal article
• Source: PARASITES & VECTORS; v. 10, JUN 6 2017.
• Web of Science Citations: 3

Abstract

Background: Infections with parasites of the Leishmania donovani complex result in clinical outcomes that range fromasymptomatic infection to severe and fatal visceral leishmaniasis (VL). Neutrophils are major players of the immune response against Leishmania, but their contribution to distinct states of infection is unknown. Gene expression data suggest the activation of the NETosis pathway during human visceral leishmaniasis. Thus, we conducted an exploratory study to evaluate NET-related molecules in retrospective sera from VL patients, asymptomatic individuals and uninfected endemic controls. Results: We demonstrate that VL patients and asymptomatic individuals exhibit differential regulation of molecules associated with neutrophil extracellular traps (NET). These differences were observed at the transcriptional level of genes encoding NET-associated proteins; in quantifications of cell free DNA and metalloproteinase 9; and in enzymatic activity of DNAse and elastase. Moreover, multivariate analysis resulted in class-specific signatures, and ROC curves demonstrate the ability of these molecules in discriminating asymptomatic infection from uninfected controls. Conclusion: Molecules that are associated with NETs are differentially regulated between distinct states of infection with L. infantum, suggesting that NETs might have distinct roles depending on the clinical status of infection. Although unlikely to be exclusive for VL, these signatures can be useful to better characterize asymptomatic infections in endemic regions of this disease. (AU)

• FAPESP's process: 14/25856-8 - The Role of IgG Fc N-Glycosylation on the Pathogenesis of Visceral Leishmaniasis: Insights Into New Strategies of Therapy
• Grantee: Luiz Gustavo Araujo Gardinassi
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/00382-0 - PROSPECTING TICK SIALOMES FOR DISCOVERY OF NEW ANTIMICROBIAL COMPONENTS
• Grantee: Gustavo Rocha Garcia
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 11/23819-0 - 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
• Grantee: Luiz Gustavo Araujo Gardinassi
• Support Opportunities: Scholarships in Brazil - Doctorate