TY - JOUR
T1 - γδ T cells and CD14+ monocytes are predominant cellular sources of cytokines and chemokines associated with severe malaria
AU - Stanisic, Danielle I
AU - Cutts, Julia
AU - Eriksson, Emily
AU - Fowkes, Freya J I
AU - Rosanas-Urgell, Anna
AU - Siba, Peter
AU - Laman, Moses
AU - Davis, Timothy M E
AU - Manning, Laurens
AU - Mueller, Ivo
AU - Schofield, Louis
N1 - © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: [email protected].
PY - 2014
Y1 - 2014
N2 - BACKGROUND: Severe malaria (SM) is associated with high levels of cytokines such as tumor necrosis factor (TNF), interleukin 1 (IL-1), and interleukin 6 (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 Plasmodium falciparum parasitized 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-1βm and MCP-2. TNF and MIP-1α were significantly higher in the SM compared to the UM group. IL-10, IL-6, MIP-1α, MIP-1β, 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-1β, and MIP-1α were produced predominantly by monocytes and γδ 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 γδ T cells. Monocyte-derived chemokines support a role for monocyte infiltrates in the etiology of SM.
AB - BACKGROUND: Severe malaria (SM) is associated with high levels of cytokines such as tumor necrosis factor (TNF), interleukin 1 (IL-1), and interleukin 6 (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 Plasmodium falciparum parasitized 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-1βm and MCP-2. TNF and MIP-1α were significantly higher in the SM compared to the UM group. IL-10, IL-6, MIP-1α, MIP-1β, 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-1β, and MIP-1α were produced predominantly by monocytes and γδ 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 γδ T cells. Monocyte-derived chemokines support a role for monocyte infiltrates in the etiology of SM.
KW - Antigens, CD14
KW - Case-Control Studies
KW - Child
KW - Child, Preschool
KW - Cytokines
KW - Female
KW - Humans
KW - Infant
KW - Malaria, Falciparum
KW - Male
KW - Monocytes
KW - Papua New Guinea
KW - Plasmodium falciparum
KW - Receptors, Antigen, T-Cell, gamma-delta
KW - T-Lymphocytes
U2 - 10.1093/infdis/jiu083
DO - 10.1093/infdis/jiu083
M3 - A1: Web of Science-article
C2 - 24523513
SN - 0022-1899
VL - 210
SP - 295
EP - 305
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 2
ER -