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gammadelta T cells and CD14+ monocytes are predominant cellular sources of cytokines and chemokines associated with severe malaria

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dc.contributor.author Stanisic, D. I. en_US
dc.contributor.author Cutts, J. en_US
dc.contributor.author Eriksson, E. en_US
dc.contributor.author Fowkes, F. J. en_US
dc.contributor.author Rosanas-Urgell, A. en_US
dc.contributor.author Siba, P. en_US
dc.contributor.author Laman, M. en_US
dc.contributor.author Davis, T. M. en_US
dc.contributor.author Manning, L. en_US
dc.contributor.author Mueller, I. en_US
dc.contributor.author Schofield, L. en_US
dc.date.accessioned 2014-09-25T13:39:59Z
dc.date.available 2014-09-25T13:39:59Z
dc.date.issued 2014 en_US
dc.identifier.issn 0022-1899 en_US
dc.identifier.doi http://dx.doi.org/10.1093/infdis/jiu083 en_US
dc.identifier.other ITG-B5A; DBM; U-MALAR; JIF; DOI; FTA; Abstract; UPD56 en_US
dc.identifier.uri http://hdl.handle.net/10390/8021
dc.description.abstract Background: Severe malaria (SM) is associated with high levels of cytokines such as TNF, IL-1 and IL-6. The role of chemokines is less clear, as is their cellular source. Methods: In a case-control study of children with SM (n=200), uncomplicated malaria (UM) (n=153) and healthy community controls (HC) (n=162) in Papua New Guinea, we measured cytokine/chemokine production by Peripheral Blood Mononuclear Cells (PBMCs) stimulated with live P. falciparum parasitised red blood cells (pRBC). Cellular sources were determined. Associations between immunological endpoints and clinical/parasitological variables were tested.Results. Compared to HC and UM, children with SM produced significantly higher IL-10, IP-10, MIP-1beta and MCP-2. TNF and MIP-1alpha were significantly higher in the SM compared to the UM group. IL-10, IL-6, MIP-1alpha, MIP-1beta and MCP-2 were associated with increased odds of SM. SM syndromes were associated with distinct cytokine/chemokine response profiles compared to UM cases. TNF, MIP-1beta and MIP-1alpha were produced predominantly by monocytes and gammadelta T cells, and IL-10 by CD4+ T cells. Conclusions: Early/innate PBMC responses to pRBC in vitro are informative as to cytokines/chemokines associated with SM. Predominant cellular sources are monocytes and gammadelta T cells. Monocyte-derived chemokines support a role for monocyte infiltrates in the aetiology of SM. en_US
dc.language English en_US
dc.subject Protozoal diseases en_US
dc.subject Malaria en_US
dc.subject Plasmodium falciparum en_US
dc.subject Vectors en_US
dc.subject Mosquitoes en_US
dc.subject Anopheles en_US
dc.subject Etiology en_US
dc.subject Peripheral blood mononuclear cell (PBMC) en_US
dc.subject Red blood cells en_US
dc.subject Cytokines en_US
dc.subject Chemokines en_US
dc.subject Cellular en_US
dc.subject IL-10 en_US
dc.subject IP-10 en_US
dc.subject MIP-10 en_US
dc.subject MCP-2 en_US
dc.subject Associations en_US
dc.subject T cells en_US
dc.subject CD4-positive-T-lymphocytes en_US
dc.subject Papua New Guinea en_US
dc.subject Pacific en_US
dc.title gammadelta T cells and CD14+ monocytes are predominant cellular sources of cytokines and chemokines associated with severe malaria en_US
dc.type Article en_US
dc.citation.issue 2 en_US
dc.citation.jtitle Journal of Infectious Diseases en_US
dc.citation.volume 210 en_US
dc.citation.pages 295-305 en_US
dc.identifier.pmid http://www.ncbi.nlm.nih.gov/pubmed/24523513 en_US
dc.citation.jabbreviation J Infect Dis en_US


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