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Stage- and Gender-Specific Proteomic Analysis of Brugia malayi Excretory-Secretory Products

Identifieur interne : 003884 ( Pmc/Checkpoint ); précédent : 003883; suivant : 003885

Stage- and Gender-Specific Proteomic Analysis of Brugia malayi Excretory-Secretory Products

Auteurs : Yovany Moreno ; Timothy G. Geary

Source :

RBID : PMC:2569413

Abstract

Introduction

While we lack a complete understanding of the molecular mechanisms by which parasites establish and achieve protection from host immune responses, it is accepted that many of these processes are mediated by products, primarily proteins, released from the parasite. Parasitic nematodes occur in different life stages and anatomical compartments within the host. Little is known about the composition and variability of products released at different developmental stages and their contribution to parasite survival and progression of the infection.

Methodology/Principal Findings

To gain a deeper understanding on these aspects, we collected and analyzed through 1D-SDS PAGE and LC-MS/MS the Excretory-Secretory Products (ESP) of adult female, adult male and microfilariae of the filarial nematode Brugia malayi, one of the etiological agents of human lymphatic filariasis. This proteomic analysis led to the identification of 228 proteins. The list includes 76 proteins with unknown function as well as also proteins with potential immunoregulatory properties, such as protease inhibitors, cytokine homologues and carbohydrate-binding proteins. Larval and adult ESP differed in composition. Only 32 proteins were shared between all three stages/genders. Consistent with this observation, different gene ontology profiles were associated with the different ESP.

Conclusions/Significance

A comparative analysis of the proteins released in vitro by different forms of a parasitic nematode dwelling in the same host is presented. The catalog of secreted proteins reflects different stage- and gender-specific related processes and different strategies of immune evasion, providing valuable insights on the contribution of each form of the parasite for establishing the host–parasite interaction.


Url:
DOI: 10.1371/journal.pntd.0000326
PubMed: 18958170
PubMed Central: 2569413


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PMC:2569413

Le document en format XML

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<p>While we lack a complete understanding of the molecular mechanisms by which parasites establish and achieve protection from host immune responses, it is accepted that many of these processes are mediated by products, primarily proteins, released from the parasite. Parasitic nematodes occur in different life stages and anatomical compartments within the host. Little is known about the composition and variability of products released at different developmental stages and their contribution to parasite survival and progression of the infection.</p>
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<title>Methodology/Principal Findings</title>
<p>To gain a deeper understanding on these aspects, we collected and analyzed through 1D-SDS PAGE and LC-MS/MS the Excretory-Secretory Products (ESP) of adult female, adult male and microfilariae of the filarial nematode
<italic>Brugia malayi</italic>
, one of the etiological agents of human lymphatic filariasis. This proteomic analysis led to the identification of 228 proteins. The list includes 76 proteins with unknown function as well as also proteins with potential immunoregulatory properties, such as protease inhibitors, cytokine homologues and carbohydrate-binding proteins. Larval and adult ESP differed in composition. Only 32 proteins were shared between all three stages/genders. Consistent with this observation, different gene ontology profiles were associated with the different ESP.</p>
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<p>A comparative analysis of the proteins released
<italic>in vitro</italic>
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Excretory-Secretory Products</article-title>
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<italic>B. malayi</italic>
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<sup>*</sup>
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<addr-line>Institute of Parasitology, McGill University, Ste-Anne-de-Bellevue, Quebec, Canada</addr-line>
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<aff id="edit1">University of Pittsburgh, United States of America</aff>
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<corresp id="cor1">* E-mail:
<email>timothy.g.geary@mcgill.ca</email>
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<p>Conceived and designed the experiments: YM TGG. Performed the experiments: YM. Analyzed the data: YM TGG. Wrote the paper: YM TGG.</p>
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<copyright-year>2008</copyright-year>
<abstract>
<sec>
<title>Introduction</title>
<p>While we lack a complete understanding of the molecular mechanisms by which parasites establish and achieve protection from host immune responses, it is accepted that many of these processes are mediated by products, primarily proteins, released from the parasite. Parasitic nematodes occur in different life stages and anatomical compartments within the host. Little is known about the composition and variability of products released at different developmental stages and their contribution to parasite survival and progression of the infection.</p>
</sec>
<sec>
<title>Methodology/Principal Findings</title>
<p>To gain a deeper understanding on these aspects, we collected and analyzed through 1D-SDS PAGE and LC-MS/MS the Excretory-Secretory Products (ESP) of adult female, adult male and microfilariae of the filarial nematode
<italic>Brugia malayi</italic>
, one of the etiological agents of human lymphatic filariasis. This proteomic analysis led to the identification of 228 proteins. The list includes 76 proteins with unknown function as well as also proteins with potential immunoregulatory properties, such as protease inhibitors, cytokine homologues and carbohydrate-binding proteins. Larval and adult ESP differed in composition. Only 32 proteins were shared between all three stages/genders. Consistent with this observation, different gene ontology profiles were associated with the different ESP.</p>
</sec>
<sec>
<title>Conclusions/Significance</title>
<p>A comparative analysis of the proteins released
<italic>in vitro</italic>
by different forms of a parasitic nematode dwelling in the same host is presented. The catalog of secreted proteins reflects different stage- and gender-specific related processes and different strategies of immune evasion, providing valuable insights on the contribution of each form of the parasite for establishing the host–parasite interaction.</p>
</sec>
</abstract>
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<title>Author Summary</title>
<p>To succeed in infection, parasites must have ways to reach the host, penetrate its tissues and escape its defense systems. As they are not necessarily fatal, most helminth parasites remain viable within their host for many years, exerting a strong influence over the host immune function. Many of these functions are performed by products that are released from the parasite. We exploited the remarkable sensitivity of modern proteomics tools together with the availability of a sequenced genome to identify and compare the proteins released
<italic>in vitro</italic>
by adult males, adult females and the microfilariae of the filarial nematode
<italic>Brugia malayi</italic>
. This parasite is one of the etiological agents of lymphatic filariasis, a disease that poses continuing and significant threats to human health. The different forms of the parasite inhabit different compartments in the mammalian host. We found that the set of proteins released by each form is unique; they must reflect particular developmental processes and different strategies for evasion of host responses. The identification of these proteins will allow us to illuminate the biology of secretory processes in this organism and to establish a path for developing an understanding of how these parasite proteins function in immune evasion events.</p>
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