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Protein biomarkers discriminate Leishmania major-infected and non-infected individuals in areas endemic for cutaneous leishmaniasis

BACKGROUND: A successful host immune response to infection is dependent upon both innate and adaptive immune effector mechanisms. Cutaneous leishmaniasis results in an adaptive Th1 CD4(+) T cell response that efficiently clears the parasite, but may also result in scaring. However the role of innate...

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Autores principales: Kammoun-Rebai, Wafa, Naouar, Ikbel, Libri, Valentina, Albert, Matthew, Louzir, Hechmi, Meddeb-Garnaoui, Amel, Duffy, Darragh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4806467/
https://www.ncbi.nlm.nih.gov/pubmed/27009263
http://dx.doi.org/10.1186/s12879-016-1458-6
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author Kammoun-Rebai, Wafa
Naouar, Ikbel
Libri, Valentina
Albert, Matthew
Louzir, Hechmi
Meddeb-Garnaoui, Amel
Duffy, Darragh
author_facet Kammoun-Rebai, Wafa
Naouar, Ikbel
Libri, Valentina
Albert, Matthew
Louzir, Hechmi
Meddeb-Garnaoui, Amel
Duffy, Darragh
author_sort Kammoun-Rebai, Wafa
collection PubMed
description BACKGROUND: A successful host immune response to infection is dependent upon both innate and adaptive immune effector mechanisms. Cutaneous leishmaniasis results in an adaptive Th1 CD4(+) T cell response that efficiently clears the parasite, but may also result in scaring. However the role of innate mechanisms during parasite clearance remains less well defined. METHODS: We examined a unique cohort of individuals, living in a Leishmania major endemic region, that were stratified among 3 distinct clinical groups in a cross-sectional study. Specifically, patients were classified either as healed (n = 17), asymptomatic (23), or naïve to infection (18) based upon the classical Leishmanin Skin Test (LST) and the presence or absence of scars. Utilizing a multiplexed immunoassay approach we characterized the induced cytokine and chemokine response to L. major. RESULTS: A subset of innate immune molecules was induced in all groups. By contrast, T cell-associated cytokines were largely induced in exposed groups as compared to L. major-infection naïve individuals. Two exceptions were IL-17A and IL-12p70, induced and not induced, respectively, in naïve individuals. In addition, GM-CSF was more strongly induced in healed patients as compared to the other two groups. Surprisingly an IL-13 response was the best cytokine for classifying previously infected donors. CONCLUSIONS: Exploratory data analysis, utilizing principle component analysis (PCA), revealed distinct patient clusters of the healed and naïve groups based on the most differentially induced proteins. Asymptomatic previously infected individuals were more difficult to assign to a particular cluster based on these induced proteins. Analysis of these proteins may enable the identification of biomarkers associated with disease, leading to a better understanding of the protective mechanisms of immune response against leishmaniasis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1458-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-48064672016-03-24 Protein biomarkers discriminate Leishmania major-infected and non-infected individuals in areas endemic for cutaneous leishmaniasis Kammoun-Rebai, Wafa Naouar, Ikbel Libri, Valentina Albert, Matthew Louzir, Hechmi Meddeb-Garnaoui, Amel Duffy, Darragh BMC Infect Dis Research Article BACKGROUND: A successful host immune response to infection is dependent upon both innate and adaptive immune effector mechanisms. Cutaneous leishmaniasis results in an adaptive Th1 CD4(+) T cell response that efficiently clears the parasite, but may also result in scaring. However the role of innate mechanisms during parasite clearance remains less well defined. METHODS: We examined a unique cohort of individuals, living in a Leishmania major endemic region, that were stratified among 3 distinct clinical groups in a cross-sectional study. Specifically, patients were classified either as healed (n = 17), asymptomatic (23), or naïve to infection (18) based upon the classical Leishmanin Skin Test (LST) and the presence or absence of scars. Utilizing a multiplexed immunoassay approach we characterized the induced cytokine and chemokine response to L. major. RESULTS: A subset of innate immune molecules was induced in all groups. By contrast, T cell-associated cytokines were largely induced in exposed groups as compared to L. major-infection naïve individuals. Two exceptions were IL-17A and IL-12p70, induced and not induced, respectively, in naïve individuals. In addition, GM-CSF was more strongly induced in healed patients as compared to the other two groups. Surprisingly an IL-13 response was the best cytokine for classifying previously infected donors. CONCLUSIONS: Exploratory data analysis, utilizing principle component analysis (PCA), revealed distinct patient clusters of the healed and naïve groups based on the most differentially induced proteins. Asymptomatic previously infected individuals were more difficult to assign to a particular cluster based on these induced proteins. Analysis of these proteins may enable the identification of biomarkers associated with disease, leading to a better understanding of the protective mechanisms of immune response against leishmaniasis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1458-6) contains supplementary material, which is available to authorized users. BioMed Central 2016-03-24 /pmc/articles/PMC4806467/ /pubmed/27009263 http://dx.doi.org/10.1186/s12879-016-1458-6 Text en © Kammoun-Rebai et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Kammoun-Rebai, Wafa
Naouar, Ikbel
Libri, Valentina
Albert, Matthew
Louzir, Hechmi
Meddeb-Garnaoui, Amel
Duffy, Darragh
Protein biomarkers discriminate Leishmania major-infected and non-infected individuals in areas endemic for cutaneous leishmaniasis
title Protein biomarkers discriminate Leishmania major-infected and non-infected individuals in areas endemic for cutaneous leishmaniasis
title_full Protein biomarkers discriminate Leishmania major-infected and non-infected individuals in areas endemic for cutaneous leishmaniasis
title_fullStr Protein biomarkers discriminate Leishmania major-infected and non-infected individuals in areas endemic for cutaneous leishmaniasis
title_full_unstemmed Protein biomarkers discriminate Leishmania major-infected and non-infected individuals in areas endemic for cutaneous leishmaniasis
title_short Protein biomarkers discriminate Leishmania major-infected and non-infected individuals in areas endemic for cutaneous leishmaniasis
title_sort protein biomarkers discriminate leishmania major-infected and non-infected individuals in areas endemic for cutaneous leishmaniasis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4806467/
https://www.ncbi.nlm.nih.gov/pubmed/27009263
http://dx.doi.org/10.1186/s12879-016-1458-6
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