Molecular signatures of neutrophil extracellular traps in human visceral leishmaniasis

• Published in: Parasites & vectors Vol. 10; no. 1; p. 285
• Main Authors: Gardinassi, Luiz Gustavo, DeSouza-Vieira, Thiago S, da Silva, Naila O, Garcia, Gustavo R, Borges, Valéria M, Campos, Roseane N S, de Almeida, Roque P, de Miranda Santos, Isabel K F, Saraiva, Elvira M
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 06.06.2017; BioMed Central; BMC
• Subjects: Activation; Adolescent; Adult; Age; Analysis; Asymptomatic infection; Care and treatment; Child; Control; Defence mechanisms; Deoxyribonuclease; Deoxyribonucleases - analysis; Deoxyribonucleic acid; Development and progression; Diseases; DNA; DNA - analysis; Elastase; Enzymatic activity; Enzyme activity; Extracellular; Extracellular matrix; Extracellular Traps - genetics; Female; Gene expression; Gene Expression Profiling; Genes; Health aspects; Humans; Immune response; Immune system; Immunity; Infections; Kala-azar; Leishmania donovani - immunology; Leishmania infantum; Leishmaniasis, Visceral - immunology; Leishmaniasis, Visceral - pathology; Leukocytes (neutrophilic); Male; Matrix Metalloproteinase 9 - analysis; Metalloproteinase; Middle Aged; Multivariate analysis; NETosis; Neutrophil extracellular traps; Neutrophils; Neutrophils - immunology; Observations; Pancreatic Elastase - analysis; Parasites; Parasitic diseases; Proteins; Regions; Retrospective Studies; Short Report; Signatures; Transcription; Tropical diseases; Tuberculosis; Vector-borne diseases; Visceral leishmaniasis; Young Adult; United States > US; Asymptomatic infection; Leishmania infantum; NETosis; Visceral leishmaniasis; Neutrophil extracellular traps
• ISSN: 1756-3305; 1756-3305
• DOI: 10.1186/s13071-017-2222-5

Infections with parasites of the Leishmania donovani complex result in clinical outcomes that range from asymptomatic 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. 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. 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.