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* Institut National de la Santé et de la Recherche Médicale Unité 547, Institut Pasteur de Lille, Lille, France;
Laboratoire des Biopuces, Institut Pasteur de Lille, Lille, France; and
GE Healthcare, Piscataway, NJ 08855
In human malaria, children suffer very high rates of morbidity and mortality. To analyze the mechanisms involved in age-dependent protection against malaria, we developed an experimental model of infection in rats, where young rats are susceptible to Plasmodium berghei and adult rats control blood parasites and survive thereafter. In this study, we showed that protection of young rats could be achievable by adoptive transfer of spleen cells from adult protected rats, among which T cells could transfer partial protection. Transcriptome analysis of spleen cells transferring immunity revealed the overexpression of genes mainly expressed by eosinophils and neutrophils. Evaluation of the role of neutrophils showed that these cells were able to transfer partial protection to young rats. This antiparasitic effect was shown to be mediated, at least in part, through the neutrophil protein-1 defensin. Further adoptive transfer experiments indicated an efficient cooperation between neutrophils and T cells in protecting all young recipients. These observations, together with those from in vitro studies in human malaria, suggest that the failure of children to control infection could be related not only to an immaturity of their adaptive immunity but also to a lack in an adequate innate immune response.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Institut National de la Santé et de la Recherche Médicale Unité 547 and Institut Pasteur de Lille. C.P. is a member of Institut Pasteur de Lille and J.K. is a member of Centre National de la Recherche Scientifique.
2 Current address: Endotis Pharma, Bioincubateur, Parc Eurasanté, 70 rue du Dr Yersin, 59120 Loos, France.
3 Address correspondence and reprint requests Dr. Jamal Khalife, Institut National de la Santé et de la Recherche Médicale Unité 547, Institut Pasteur de Lille, 1 rue du Prof. Calmette, 59019 Lille, France. E-mail address: jamal.khalife{at}pasteur-lille.fr
4 Abbreviations used in this paper: NP-1, neutrophil protein-1; p.i., postinfection; Q-PCR, quantitative PCR; Ct, cycle threshold; PGRP, peptidoglycan recognition protein; MMP9, matrix metalloproteinase 9; PRG2, proteoglycan 2; MBP, major basic protein; NRAMP1, natural resistance-associated macrophage protein 1; Hp, haptoglobin.
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