Synthetic Plasmodium-like hemozoin activates the immune response: a morphology - function study.

Increasing evidence points to an important role for hemozoin (HZ), the malaria pigment, in the immunopathology related to this infection. However, there is no consensus as to whether HZ exerts its immunostimulatory activity in absence of other parasite or host components. Contamination of native HZ...

Full description

Bibliographic Details
Main Authors: Maritza Jaramillo, Marie-Josée Bellemare, Caroline Martel, Marina Tiemi Shio, Ana Paulina Contreras, Marianne Godbout, Michel Roger, Eric Gaudreault, Jean Gosselin, D Scott Bohle, Martin Olivier
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2009-09-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC2734055?pdf=render
_version_ 1828392838572802048
author Maritza Jaramillo
Marie-Josée Bellemare
Caroline Martel
Marina Tiemi Shio
Ana Paulina Contreras
Marianne Godbout
Michel Roger
Eric Gaudreault
Jean Gosselin
D Scott Bohle
Martin Olivier
author_facet Maritza Jaramillo
Marie-Josée Bellemare
Caroline Martel
Marina Tiemi Shio
Ana Paulina Contreras
Marianne Godbout
Michel Roger
Eric Gaudreault
Jean Gosselin
D Scott Bohle
Martin Olivier
author_sort Maritza Jaramillo
collection DOAJ
description Increasing evidence points to an important role for hemozoin (HZ), the malaria pigment, in the immunopathology related to this infection. However, there is no consensus as to whether HZ exerts its immunostimulatory activity in absence of other parasite or host components. Contamination of native HZ preparations and the lack of a unified protocol to produce crystals that mimic those of Plasmodium HZ (PHZ) are major technical limitants when performing functional studies with HZ. In fact, the most commonly used methods generate a heterogeneous nanocrystalline material. Thus, it is likely that such aggregates do not resemble to PHZ and differ in their inflammatory properties. To address this issue, the present study was designed to establish whether synthetic HZ (sHZ) crystals produced by different methods vary in their morphology and in their ability to activate immune responses. We report a new method of HZ synthesis (the precise aqueous acid-catalyzed method) that yields homogeneous sHZ crystals (Plasmodium-like HZ) which are very similar to PHZ in their size and physicochemical properties. Importantly, these crystals are devoid of protein and DNA contamination. Of interest, structure-function studies revealed that the size and shape of the synthetic crystals influences their ability to activate inflammatory responses (e.g. nitric oxide, chemokine and cytokine mRNA) in vitro and in vivo. In summary, our data confirm that sHZ possesses immunostimulatory properties and underline the importance of verifying by electron microscopy both the morphology and homogeneity of the synthetic crystals to ensure that they closely resemble those of the parasite. Periodic quality control experiments and unification of the method of HZ synthesis are key steps to unravel the role of HZ in malaria immunopathology.
first_indexed 2024-12-10T07:28:26Z
format Article
id doaj.art-49251ef6b71f4f72972fee16f4f1b91e
institution Directory Open Access Journal
issn 1932-6203
language English
last_indexed 2024-12-10T07:28:26Z
publishDate 2009-09-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj.art-49251ef6b71f4f72972fee16f4f1b91e2022-12-22T01:57:39ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-09-0149e695710.1371/journal.pone.0006957Synthetic Plasmodium-like hemozoin activates the immune response: a morphology - function study.Maritza JaramilloMarie-Josée BellemareCaroline MartelMarina Tiemi ShioAna Paulina ContrerasMarianne GodboutMichel RogerEric GaudreaultJean GosselinD Scott BohleMartin OlivierIncreasing evidence points to an important role for hemozoin (HZ), the malaria pigment, in the immunopathology related to this infection. However, there is no consensus as to whether HZ exerts its immunostimulatory activity in absence of other parasite or host components. Contamination of native HZ preparations and the lack of a unified protocol to produce crystals that mimic those of Plasmodium HZ (PHZ) are major technical limitants when performing functional studies with HZ. In fact, the most commonly used methods generate a heterogeneous nanocrystalline material. Thus, it is likely that such aggregates do not resemble to PHZ and differ in their inflammatory properties. To address this issue, the present study was designed to establish whether synthetic HZ (sHZ) crystals produced by different methods vary in their morphology and in their ability to activate immune responses. We report a new method of HZ synthesis (the precise aqueous acid-catalyzed method) that yields homogeneous sHZ crystals (Plasmodium-like HZ) which are very similar to PHZ in their size and physicochemical properties. Importantly, these crystals are devoid of protein and DNA contamination. Of interest, structure-function studies revealed that the size and shape of the synthetic crystals influences their ability to activate inflammatory responses (e.g. nitric oxide, chemokine and cytokine mRNA) in vitro and in vivo. In summary, our data confirm that sHZ possesses immunostimulatory properties and underline the importance of verifying by electron microscopy both the morphology and homogeneity of the synthetic crystals to ensure that they closely resemble those of the parasite. Periodic quality control experiments and unification of the method of HZ synthesis are key steps to unravel the role of HZ in malaria immunopathology.http://europepmc.org/articles/PMC2734055?pdf=render
spellingShingle Maritza Jaramillo
Marie-Josée Bellemare
Caroline Martel
Marina Tiemi Shio
Ana Paulina Contreras
Marianne Godbout
Michel Roger
Eric Gaudreault
Jean Gosselin
D Scott Bohle
Martin Olivier
Synthetic Plasmodium-like hemozoin activates the immune response: a morphology - function study.
PLoS ONE
title Synthetic Plasmodium-like hemozoin activates the immune response: a morphology - function study.
title_full Synthetic Plasmodium-like hemozoin activates the immune response: a morphology - function study.
title_fullStr Synthetic Plasmodium-like hemozoin activates the immune response: a morphology - function study.
title_full_unstemmed Synthetic Plasmodium-like hemozoin activates the immune response: a morphology - function study.
title_short Synthetic Plasmodium-like hemozoin activates the immune response: a morphology - function study.
title_sort synthetic plasmodium like hemozoin activates the immune response a morphology function study
url http://europepmc.org/articles/PMC2734055?pdf=render
work_keys_str_mv AT maritzajaramillo syntheticplasmodiumlikehemozoinactivatestheimmuneresponseamorphologyfunctionstudy
AT mariejoseebellemare syntheticplasmodiumlikehemozoinactivatestheimmuneresponseamorphologyfunctionstudy
AT carolinemartel syntheticplasmodiumlikehemozoinactivatestheimmuneresponseamorphologyfunctionstudy
AT marinatiemishio syntheticplasmodiumlikehemozoinactivatestheimmuneresponseamorphologyfunctionstudy
AT anapaulinacontreras syntheticplasmodiumlikehemozoinactivatestheimmuneresponseamorphologyfunctionstudy
AT mariannegodbout syntheticplasmodiumlikehemozoinactivatestheimmuneresponseamorphologyfunctionstudy
AT michelroger syntheticplasmodiumlikehemozoinactivatestheimmuneresponseamorphologyfunctionstudy
AT ericgaudreault syntheticplasmodiumlikehemozoinactivatestheimmuneresponseamorphologyfunctionstudy
AT jeangosselin syntheticplasmodiumlikehemozoinactivatestheimmuneresponseamorphologyfunctionstudy
AT dscottbohle syntheticplasmodiumlikehemozoinactivatestheimmuneresponseamorphologyfunctionstudy
AT martinolivier syntheticplasmodiumlikehemozoinactivatestheimmuneresponseamorphologyfunctionstudy