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J Infect Dis. 2014 Jul 15;210(2):295-305. doi: 10.1093/infdis/jiu083. Epub 2014 Feb 12.

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

Author information

  • 1Division of Infection and Immunity, Walter and Eliza Hall Institute, Parkville, Victoria, Australia Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea.
  • 2Division of Infection and Immunity, Walter and Eliza Hall Institute, Parkville, Victoria, Australia.
  • 3Division of Infection and Immunity, Walter and Eliza Hall Institute, Parkville, Victoria, Australia Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
  • 4Burnet Institute for Medical Research and Public Health, Prahan, Victoria, Australia.
  • 5Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea.
  • 6Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea School of Medicine and Pharmacology, University of Western Australia, Fremantle Hospital, Fremantle, Western Australia, Australia.
  • 7School of Medicine and Pharmacology, University of Western Australia, Fremantle Hospital, Fremantle, Western Australia, Australia.
  • 8Division of Infection and Immunity, Walter and Eliza Hall Institute, Parkville, Victoria, Australia Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea Center de Recerca en Salut Internacional de Barcelona (CRESIB), Barcelona, Spain.
  • 9Division of Infection and Immunity, Walter and Eliza Hall Institute, Parkville, Victoria, Australia Australian Institute of Tropical Health and Medicine, James Cook University, Queensland, Australia.

Abstract

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.

© 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: journals.permissions@oup.com.

KEYWORDS:

chemokines; cytokines; monocyte/macrophages; severe malaria; γδ T cells

PMID:
24523513
[PubMed - indexed for MEDLINE]
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