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1.
Am J Trop Med Hyg ; 74(4): 578-84, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16606987

RESUMO

The high frequencies of both alpha+ thalassemia and the sickle cell trait (hemoglobin AS [HbAS]) found in many tropical populations are thought to reflect selection pressure from Plasmodium falciparum malaria. For HbAS, but not for alpha+ thalassemia, protection appears to be mediated by the enhanced phagocytic clearance of ring-infected erythrocytes. We have investigated the genotype-specific distributions of peripheral blood leukocyte populations in two groups of children living on the coast of Kenya: a group of healthy P. falciparum parasite-negative children sampled at cross-sectional survey during a period of low malaria transmission, and a group of children attending the hospital with acute malaria. We report distinctive distributions of peripheral blood myeloid dendritic cells and monocytes in children with alpha+ thalassemia and HbAS during healthy periods and disease, and suggest ways in which these might relate to the mechanisms of protection afforded by these conditions.


Assuntos
Malária Falciparum/genética , Células Mieloides/citologia , Traço Falciforme/genética , Talassemia alfa/genética , Criança , Pré-Escolar , Estudos Transversais , Feminino , Citometria de Fluxo , Genótipo , Hemoglobina Falciforme/genética , Humanos , Lactente , Quênia/epidemiologia , Malária Falciparum/sangue , Malária Falciparum/complicações , Malária Falciparum/epidemiologia , Masculino , Traço Falciforme/sangue , Traço Falciforme/complicações , Traço Falciforme/epidemiologia , Talassemia alfa/sangue , Talassemia alfa/complicações , Talassemia alfa/epidemiologia
2.
J Infect Dis ; 195(6): 905-12, 2007 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-17299722

RESUMO

BACKGROUND: Macrophage-migration inhibitory factor (MIF), one of the first cytokines described, has a broad range of proinflammatory properties. The genome sequencing project of Plasmodium falciparum identified a parasite homologue of MIF. The protein is expressed during the asexual blood stages of the parasite life cycle that cause malarial disease. The identification of a parasite homologue of MIF raised the question of whether it affects monocyte function in a manner similar to its human counterpart. METHODS: Recombinant P. falciparum MIF (PfMIF) was generated and used in vitro to assess its influence on monocyte function. Antibodies generated against PfMIF were used to determine the expression profile and localization of the protein in blood-stage parasites. Antibody responses to PfMIF were determined in Kenyan children with acute malaria and in control subjects. RESULTS: PfMIF protein was expressed in asexual blood-stage parasites, localized to the Maurer's cleft. In vitro treatment of monocytes with PfMIF inhibited random migration and reduced the surface expression of Toll-like receptor (TLR) 2, TLR4, and CD86. CONCLUSIONS: These results indicate that PfMIF is released during blood-stage malaria and potentially modulates the function of monocytes during acute P. falciparum infection.


Assuntos
Oxirredutases Intramoleculares/química , Fatores Inibidores da Migração de Macrófagos/química , Plasmodium falciparum/fisiologia , Proteínas de Protozoários/química , Animais , Formação de Anticorpos , Northern Blotting , Clonagem Molecular , Primers do DNA , Ensaio de Imunoadsorção Enzimática , Eritrócitos/parasitologia , Humanos , Inflamação , Oxirredutases Intramoleculares/imunologia , Oxirredutases Intramoleculares/isolamento & purificação , Fatores Inibidores da Migração de Macrófagos/genética , Fatores Inibidores da Migração de Macrófagos/imunologia , Fatores Inibidores da Migração de Macrófagos/isolamento & purificação , Malária Falciparum/epidemiologia , Malária Falciparum/fisiopatologia , Monócitos/parasitologia , Proteínas de Protozoários/genética , Proteínas de Protozoários/imunologia , Proteínas de Protozoários/isolamento & purificação
3.
Infect Immun ; 74(12): 6700-6, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17000725

RESUMO

The ability of Plasmodium falciparum-infected erythrocytes to adhere to host endothelial cells via receptor molecules such as ICAM-1 and CD36 is considered a hallmark for the development of severe malaria syndromes. These molecules are also expressed on leukocytes such as dendritic cells. Dendritic cells are antigen-presenting cells that are crucial for the initiation of adaptive immune responses. In many human diseases, their frequency and function is perturbed. We analyzed the frequency of peripheral blood dendritic cell subsets and the plasma concentrations of interleukin-10 (IL-10) and IL-12 in Kenyan children with severe malaria and during convalescence and related these parameters to the adhesion phenotype of the acute parasite isolates. The frequency of CD1c(+) dendritic cells in children with acute malaria was comparable to that in healthy controls, but the frequency of BDCA3(+) dendritic cells was significantly increased. Analysis of the adhesion phenotypes of parasite isolates revealed that adhesion to ICAM-1 was associated with the frequency of peripheral blood CD1c(+) dendritic cells, whereas the adhesion of infected erythrocytes to CD36 correlated with high concentrations of IL-10 and low concentrations of IL-12 in plasma.


Assuntos
Antígenos de Superfície/análise , Células Dendríticas/imunologia , Malária Falciparum/imunologia , Plasmodium falciparum , Animais , Apresentação de Antígeno , Antígenos CD1/análise , Circulação Sanguínea , Antígenos CD36/imunologia , Adesão Celular , Contagem de Células , Pré-Escolar , Eritrócitos/imunologia , Eritrócitos/parasitologia , Glicoproteínas/análise , Humanos , Molécula 1 de Adesão Intercelular/imunologia , Interleucina-10/sangue , Interleucina-12/sangue , Quênia , Leucócitos Mononucleares/imunologia , Trombomodulina
4.
J Infect Dis ; 191(10): 1599-611, 2005 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-15838786

RESUMO

Malaria is a global problem, and there is a critical need for further understanding of the disease process. When malarial parasites invade and develop within the bloodstream, they stimulate a profound host response whose main clinical sign is fever. To explore this response, we measured host gene expression in whole blood from Kenyan children hospitalized with either acute malaria or other febrile illnesses. Genomewide analysis of expression identified 2 principal gene-expression profiles related to neutrophil and erythroid activity. In addition to these general acute responses, a third gene-expression profile was associated with host parasitemia; mediators of erythrophagocytosis and cellular stress were notable components of this response. The delineation of subjects on the basis of patterns of gene expression provides a molecular perspective of the host response to malaria and further functional insight into the underlying processes of pathogenesis.


Assuntos
Expressão Gênica , Malária/sangue , Criança , Pré-Escolar , Eritrócitos/metabolismo , Feminino , Expressão Gênica/imunologia , Perfilação da Expressão Gênica , Humanos , Lactente , Quênia , Contagem de Leucócitos , Malária/imunologia , Masculino , Neutrófilos/metabolismo , Parasitemia , Fenótipo
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