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Cellular Markers of Active Disease and Cure in Different Forms of Leishmania infantum-Induced Disease

Increased numbers of peripheral blood mononucleocytes (PBMC) and increased IFN-γ secretion following in vitro challenge of blood samples with soluble Leishmania antigen (SLA), have been proposed as biomarkers of specific cell-mediated immunity, indicating that treatment of visceral leishmaniasis (VL...

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Autores principales: Botana, Laura, Matía, Belén, San Martin, Juan V., Romero-Maté, Alberto, Castro, Alicia, Molina, Laura, Fernandez, Laura, Ibarra-Meneses, Ana, Aguado, Marta, Sánchez, Carmen, Horrillo, Luis, Chicharro, Carmen, Nieto, Javier, Ortega, Sheila, Ruiz-Giardin, José Manuel, Carrillo, Eugenia, Moreno, Javier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6243388/
https://www.ncbi.nlm.nih.gov/pubmed/30483480
http://dx.doi.org/10.3389/fcimb.2018.00381
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author Botana, Laura
Matía, Belén
San Martin, Juan V.
Romero-Maté, Alberto
Castro, Alicia
Molina, Laura
Fernandez, Laura
Ibarra-Meneses, Ana
Aguado, Marta
Sánchez, Carmen
Horrillo, Luis
Chicharro, Carmen
Nieto, Javier
Ortega, Sheila
Ruiz-Giardin, José Manuel
Carrillo, Eugenia
Moreno, Javier
author_facet Botana, Laura
Matía, Belén
San Martin, Juan V.
Romero-Maté, Alberto
Castro, Alicia
Molina, Laura
Fernandez, Laura
Ibarra-Meneses, Ana
Aguado, Marta
Sánchez, Carmen
Horrillo, Luis
Chicharro, Carmen
Nieto, Javier
Ortega, Sheila
Ruiz-Giardin, José Manuel
Carrillo, Eugenia
Moreno, Javier
author_sort Botana, Laura
collection PubMed
description Increased numbers of peripheral blood mononucleocytes (PBMC) and increased IFN-γ secretion following in vitro challenge of blood samples with soluble Leishmania antigen (SLA), have been proposed as biomarkers of specific cell-mediated immunity, indicating that treatment of visceral leishmaniasis (VL) has been successful. However, Leishmania infantum infection may manifest as cutaneous leishmaniasis (CL), and less commonly as localized leishmanial lymphadenopathy (LLL) or mucosal leishmaniasis (ML). The present work examines the value of these biomarkers as indicators of cured leishmaniasis presenting in these different forms. Blood samples were collected before and after treatment from patients living in Fuenlabrada (Madrid, Spain), an L. infantum-endemic area recently the center of a leishmaniasis outbreak. All samples were subjected to Leishmania-specific PCR, serological tests (IFAT and rK39-ICT), and the SLA-cell proliferation assay (SLA-CPA), recording PBMC proliferation and the associated changes in IFN-γ production. Differences in the results recorded for the active and cured conditions were only significant for VL. PCR returned positive results in 67% of patients with active VL and in 3% of those with cured leishmaniasis. Similarly, rK39-ICT returned a positive result in 77% of active VL samples vs. 52% in cured VL samples, and IFAT in 90% vs. 56%; in the SLA-CPA, PBMC proliferation was seen in 16% vs. 90%, and an associated increase in IFN-γ production of 14 and 84%, respectively. The present findings reinforce the idea that PBMC proliferation and increased IFN-γ production in SLA-stimulated PBMC provide biomarkers of clinical cure in VL. Other tests are urgently needed to distinguish between the cured and active forms of the other types of clinical leishmaniasis caused by L. infantum.
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spelling pubmed-62433882018-11-27 Cellular Markers of Active Disease and Cure in Different Forms of Leishmania infantum-Induced Disease Botana, Laura Matía, Belén San Martin, Juan V. Romero-Maté, Alberto Castro, Alicia Molina, Laura Fernandez, Laura Ibarra-Meneses, Ana Aguado, Marta Sánchez, Carmen Horrillo, Luis Chicharro, Carmen Nieto, Javier Ortega, Sheila Ruiz-Giardin, José Manuel Carrillo, Eugenia Moreno, Javier Front Cell Infect Microbiol Cellular and Infection Microbiology Increased numbers of peripheral blood mononucleocytes (PBMC) and increased IFN-γ secretion following in vitro challenge of blood samples with soluble Leishmania antigen (SLA), have been proposed as biomarkers of specific cell-mediated immunity, indicating that treatment of visceral leishmaniasis (VL) has been successful. However, Leishmania infantum infection may manifest as cutaneous leishmaniasis (CL), and less commonly as localized leishmanial lymphadenopathy (LLL) or mucosal leishmaniasis (ML). The present work examines the value of these biomarkers as indicators of cured leishmaniasis presenting in these different forms. Blood samples were collected before and after treatment from patients living in Fuenlabrada (Madrid, Spain), an L. infantum-endemic area recently the center of a leishmaniasis outbreak. All samples were subjected to Leishmania-specific PCR, serological tests (IFAT and rK39-ICT), and the SLA-cell proliferation assay (SLA-CPA), recording PBMC proliferation and the associated changes in IFN-γ production. Differences in the results recorded for the active and cured conditions were only significant for VL. PCR returned positive results in 67% of patients with active VL and in 3% of those with cured leishmaniasis. Similarly, rK39-ICT returned a positive result in 77% of active VL samples vs. 52% in cured VL samples, and IFAT in 90% vs. 56%; in the SLA-CPA, PBMC proliferation was seen in 16% vs. 90%, and an associated increase in IFN-γ production of 14 and 84%, respectively. The present findings reinforce the idea that PBMC proliferation and increased IFN-γ production in SLA-stimulated PBMC provide biomarkers of clinical cure in VL. Other tests are urgently needed to distinguish between the cured and active forms of the other types of clinical leishmaniasis caused by L. infantum. Frontiers Media S.A. 2018-11-13 /pmc/articles/PMC6243388/ /pubmed/30483480 http://dx.doi.org/10.3389/fcimb.2018.00381 Text en Copyright © 2018 Botana, Matía, San Martin, Romero-Maté, Castro, Molina, Fernandez, Ibarra-Meneses, Aguado, Sánchez, Horrillo, Chicharro, Nieto, Ortega, Ruiz-Giardin, Carrillo and Moreno. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Botana, Laura
Matía, Belén
San Martin, Juan V.
Romero-Maté, Alberto
Castro, Alicia
Molina, Laura
Fernandez, Laura
Ibarra-Meneses, Ana
Aguado, Marta
Sánchez, Carmen
Horrillo, Luis
Chicharro, Carmen
Nieto, Javier
Ortega, Sheila
Ruiz-Giardin, José Manuel
Carrillo, Eugenia
Moreno, Javier
Cellular Markers of Active Disease and Cure in Different Forms of Leishmania infantum-Induced Disease
title Cellular Markers of Active Disease and Cure in Different Forms of Leishmania infantum-Induced Disease
title_full Cellular Markers of Active Disease and Cure in Different Forms of Leishmania infantum-Induced Disease
title_fullStr Cellular Markers of Active Disease and Cure in Different Forms of Leishmania infantum-Induced Disease
title_full_unstemmed Cellular Markers of Active Disease and Cure in Different Forms of Leishmania infantum-Induced Disease
title_short Cellular Markers of Active Disease and Cure in Different Forms of Leishmania infantum-Induced Disease
title_sort cellular markers of active disease and cure in different forms of leishmania infantum-induced disease
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6243388/
https://www.ncbi.nlm.nih.gov/pubmed/30483480
http://dx.doi.org/10.3389/fcimb.2018.00381
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