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Intraspecies Polymorphisms in the Lipophosphoglycan of L. braziliensis Differentially Modulate Macrophage Activation via TLR4
Lipophosphoglycan (LPG) is the major Leishmania surface glycoconjugate having importance during the host-parasite interface. Leishmania (Viannia) braziliensis displays a spectrum of clinical forms including: typical cutaneous leishmaniasis (TL), mucocutaneous (ML), and atypical lesions (AL). Those v...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6636203/ https://www.ncbi.nlm.nih.gov/pubmed/31355149 http://dx.doi.org/10.3389/fcimb.2019.00240 |
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author | Vieira, Tamara da Silva Rugani, Jeronimo Nunes Nogueira, Paula Monalisa Torrecilhas, Ana Cláudia Gontijo, Celia Maria Ferreira Descoteaux, Albert Soares, Rodrigo Pedro |
author_facet | Vieira, Tamara da Silva Rugani, Jeronimo Nunes Nogueira, Paula Monalisa Torrecilhas, Ana Cláudia Gontijo, Celia Maria Ferreira Descoteaux, Albert Soares, Rodrigo Pedro |
author_sort | Vieira, Tamara da Silva |
collection | PubMed |
description | Lipophosphoglycan (LPG) is the major Leishmania surface glycoconjugate having importance during the host-parasite interface. Leishmania (Viannia) braziliensis displays a spectrum of clinical forms including: typical cutaneous leishmaniasis (TL), mucocutaneous (ML), and atypical lesions (AL). Those variations in the immunopathology may be a result of intraspecies polymorphisms in the parasite's virulence factors. In this context, we evaluated the role of LPG of strains originated from patients with different clinical manifestations and the sandfly vector. Six isolates of L. braziliensis were used: M2903, RR051 and RR418 (TL), RR410 (AL), M15991 (ML), and M8401 (vector). LPGs were extracted and purified by hydrophobic interaction. Peritoneal macrophages from C57BL/6 and respective knock-outs (TLR2(−/−) and TLR-4(−/−)) were primed with IFN-γ and exposed to different LPGs for nitric oxide (NO) and cytokine production (IL-1β, IL-6, IL-12, and TNF-α). LPGs differentially activated the production of NO and cytokines via TLR4. In order to ascertain if such functional variations were related to intraspecies polymorphisms in the LPG, the purified glycoconjugates were subjected to western blot with specific LPG antibodies (CA7AE and LT22). Based on antibody reactivity preliminary variations in the repeat units were detected. To confirm these findings, LPGs were depolymerized for purification of repeat units. After thin layer chromatography, intraspecies polymorphisms were confirmed especially in the type and/size of sugars branching-off the repeat units motif. In conclusion, different isolates of L. braziliensis from different clinical forms and hosts possess polymorphisms in their LPGs that functionally affected macrophage responses. |
format | Online Article Text |
id | pubmed-6636203 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-66362032019-07-26 Intraspecies Polymorphisms in the Lipophosphoglycan of L. braziliensis Differentially Modulate Macrophage Activation via TLR4 Vieira, Tamara da Silva Rugani, Jeronimo Nunes Nogueira, Paula Monalisa Torrecilhas, Ana Cláudia Gontijo, Celia Maria Ferreira Descoteaux, Albert Soares, Rodrigo Pedro Front Cell Infect Microbiol Cellular and Infection Microbiology Lipophosphoglycan (LPG) is the major Leishmania surface glycoconjugate having importance during the host-parasite interface. Leishmania (Viannia) braziliensis displays a spectrum of clinical forms including: typical cutaneous leishmaniasis (TL), mucocutaneous (ML), and atypical lesions (AL). Those variations in the immunopathology may be a result of intraspecies polymorphisms in the parasite's virulence factors. In this context, we evaluated the role of LPG of strains originated from patients with different clinical manifestations and the sandfly vector. Six isolates of L. braziliensis were used: M2903, RR051 and RR418 (TL), RR410 (AL), M15991 (ML), and M8401 (vector). LPGs were extracted and purified by hydrophobic interaction. Peritoneal macrophages from C57BL/6 and respective knock-outs (TLR2(−/−) and TLR-4(−/−)) were primed with IFN-γ and exposed to different LPGs for nitric oxide (NO) and cytokine production (IL-1β, IL-6, IL-12, and TNF-α). LPGs differentially activated the production of NO and cytokines via TLR4. In order to ascertain if such functional variations were related to intraspecies polymorphisms in the LPG, the purified glycoconjugates were subjected to western blot with specific LPG antibodies (CA7AE and LT22). Based on antibody reactivity preliminary variations in the repeat units were detected. To confirm these findings, LPGs were depolymerized for purification of repeat units. After thin layer chromatography, intraspecies polymorphisms were confirmed especially in the type and/size of sugars branching-off the repeat units motif. In conclusion, different isolates of L. braziliensis from different clinical forms and hosts possess polymorphisms in their LPGs that functionally affected macrophage responses. Frontiers Media S.A. 2019-07-10 /pmc/articles/PMC6636203/ /pubmed/31355149 http://dx.doi.org/10.3389/fcimb.2019.00240 Text en Copyright © 2019 Vieira, Rugani, Nogueira, Torrecilhas, Gontijo, Descoteaux and Soares. 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 Vieira, Tamara da Silva Rugani, Jeronimo Nunes Nogueira, Paula Monalisa Torrecilhas, Ana Cláudia Gontijo, Celia Maria Ferreira Descoteaux, Albert Soares, Rodrigo Pedro Intraspecies Polymorphisms in the Lipophosphoglycan of L. braziliensis Differentially Modulate Macrophage Activation via TLR4 |
title | Intraspecies Polymorphisms in the Lipophosphoglycan of L. braziliensis Differentially Modulate Macrophage Activation via TLR4 |
title_full | Intraspecies Polymorphisms in the Lipophosphoglycan of L. braziliensis Differentially Modulate Macrophage Activation via TLR4 |
title_fullStr | Intraspecies Polymorphisms in the Lipophosphoglycan of L. braziliensis Differentially Modulate Macrophage Activation via TLR4 |
title_full_unstemmed | Intraspecies Polymorphisms in the Lipophosphoglycan of L. braziliensis Differentially Modulate Macrophage Activation via TLR4 |
title_short | Intraspecies Polymorphisms in the Lipophosphoglycan of L. braziliensis Differentially Modulate Macrophage Activation via TLR4 |
title_sort | intraspecies polymorphisms in the lipophosphoglycan of l. braziliensis differentially modulate macrophage activation via tlr4 |
topic | Cellular and Infection Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6636203/ https://www.ncbi.nlm.nih.gov/pubmed/31355149 http://dx.doi.org/10.3389/fcimb.2019.00240 |
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