Research Article: Regulation of Leishmania (L.) amazonensis Protein Expression by Host T Cell Dependent Responses: Differential Expression of Oligopeptidase B, Tryparedoxin Peroxidase and HSP70 Isoforms in Amastigotes Isolated from BALB/c and BALB/c Nude Mice

Date Published: February 18, 2015

Publisher: Public Library of Science

Author(s): Priscila Camillo Teixeira, Leonardo Garcia Velasquez, Ana Paula Lepique, Eloiza de Rezende, José Matheus Camargo Bonatto, Marcello Andre Barcinski, Edecio Cunha-Neto, Beatriz Simonsen Stolf, Mary Ann McDowell.

Abstract: Leishmaniasis is an important disease that affects 12 million people in 88 countries, with 2 million new cases every year. Leishmania amazonensis is an important agent in Brazil, leading to clinical forms varying from localized (LCL) to diffuse cutaneous leishmaniasis (DCL). One interesting issue rarely analyzed is how host immune response affects Leishmania phenotype and virulence. Aiming to study the effect of host immune system on Leishmania proteins we compared proteomes of amastigotes isolated from BALB/c and BALB/c nude mice. The athymic nude mice may resemble patients with diffuse cutaneous leishmaniasis, considered T-cell hyposensitive or anergic to Leishmania´s antigens. This work is the first to compare modifications in amastigotes’ proteomes driven by host immune response. Among the 44 differentially expressed spots, there were proteins related to oxidative/nitrosative stress and proteases. Some correspond to known Leishmania virulence factors such as OPB and tryparedoxin peroxidase. Specific isoforms of these two proteins were increased in parasites from nude mice, suggesting that T cells probably restrain their posttranslational modifications in BALB/c mice. On the other hand, an isoform of HSP70 was increased in amastigotes from BALB/c mice. We believe our study may allow identification of potential virulence factors and ways of regulating their expression.

Partial Text: Leishmaniasis is an important disease that affects 12 million people in 88 different countries in Europe, Africa, Asia and America, and 2 million new cases are reported every year (WHO 2004; [1,2]. There are different forms of tegumentary and visceral leishmaniasis, that depend on the Leishmania species and on the genetic/immunologic status of the host, all transmitted to man by the bite of naturally infected species of phlebotomine sand flies [3].

Interaction between pathogens and their hosts derives from long term co-existence. Intracelular pathogens such as Leishmania respond to an aggressive microenvironment in the host creating evasion mechanisms that guarantee their survival. To further explore the adaptation between Leishmania and its host, we have studied the protein expression profile of parasites harvested from footpad infections in immunocompetent BALB/c mice, and immunodeficient BALB/c nude mice. Our results indicate that there may be a correlation between the cellular immune response of the host and specific protein isoforms of the parasite.



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