Pretreatment with Cry1Ac Protoxin Modulates the Immune Response, and Increases the Survival ofPlasmodium-Infected CBA/Ca Mice

Martha Legorreta-Herrera,Leticia Moreno-Fierros,Rodrigo Oviedo Meza

doi:10.1155/2010/198921

Martha Legorreta-Herrera, Leticia Moreno-Fierros + Show 1 more

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https://doi.org/10.1155/2010/198921

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Abstract

Malaria is a major global health problem that kills 1-2 million people each year. Despite exhaustive research, naturally acquired immunity is poorly understood. Cry1A proteins are potent immunogens with adjuvant properties and are able to induce strong cellular and humoral responses. In fact, it has been shown that administration of Cry1Ac protoxin alone or with amoebic lysates induces protection against the lethal infection caused by the protozoa Naegleria fowleri. In this work, we studied whether Cry1Ac is able to activate the innate immune response to induce protection against Plasmodium berghei ANKA (lethal) and P. chabaudi AS (nonlethal) parasites in CBA/Ca mice. Treatment with Cry1Ac induced protection against both Plasmodium species in terms of reduced parasitaemia, longer survival time, modulation of pro- and anti-inflammatory cytokines, and increased levels of specific antibodies against Plasmodium. Understanding how to boost innate immunity to Plasmodium infection should lead to immunologically based intervention strategies.

Highlights

Each year, malaria infects approximately 500 million people and kills one to two million people, mainly children below the age of five years [1]
Our results demonstrate that administration of the Cry1Ac protoxin from B. thuringiensis induces protection against the malaria parasite when it is administered in CBA/Ca mice before infection with P. chabaudi AS and induces a longer survival time in P. berghei ANKA-infected mice (Figures 1 and 2)
Cry1Ac protoxin modulated the mRNA expression of proinflammatory cytokines, such as IFN-γ and TGF-β, and increased the levels of IgG and IgM in both P. berghei ANKA- and P. chabaudi AS-infected mice

Summary

Introduction

Malaria infects approximately 500 million people and kills one to two million people, mainly children below the age of five years [1]. It is believed that the initial interaction of the parasitised red blood cells with the host immune system is one of the most important factors in determining the nature of the subsequent innate and acquired response, and in determining whether or not severe pathology, such as cerebral malaria, severe anaemia, or cachexia, results [7,8,9]. The activated toxin, which is not toxic to vertebrates, binds to specific receptors on the brush-border membrane surface of the midgut epithelium of the insect, inducing the formation of pores and eventually leading to insect mortality [10]. Cry1Ac is a pore-forming protein that is toxic to lepidopteran insect larvae and acts by binding to the cell-surface receptor aminopeptidase N in the Manduca sexta midgut via the sugar N-acetyl-Dgalactosamine (GalNAc) [11, 12]

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