Contribution of T cells and neutrophils in protection of young susceptible rats from fatal experimental malaria.
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.
Pierrot
Christine
C
Institut National de la Santé et de la Recherche Médicale Unité 547, Institut Pasteur de Lille, Lille, France.
Adam
Estelle
E
Hot
David
D
Lafitte
Sophia
S
Capron
Monique
M
George
James D
JD
Khalife
Jamal
J
D019264:Adoptive Transfer; D000367:Age Factors; D000818:Animals; D004195:Disease Models, Animal; D008288:Malaria / Q000276:immunology* / Q000628:therapy; D009504:Neutrophils / Q000276:immunology* / Q000469:parasitology; D010962:Plasmodium berghei; D051381:Rats; D013154:Spleen / Q000166:cytology; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology* / Q000469:parasitology / Q000637:transplantation; D023084:alpha-Defensins / Q000276:immunology*
D023084:alpha-Defensins; C406564:defensin NP-1