Malaria blood stage parasites activate human plasmacytoid dendritic cells and murine dendritic cells through a Toll-like receptor 9-dependent pathway - PubMed (original) (raw)
. 2004 Apr 15;172(8):4926-33.
doi: 10.4049/jimmunol.172.8.4926.
Kosol Yongvanitchit, Utaiwan Kum-arb, Hiroaki Hemmi, Shizuo Akira, Arthur M Krieg, D Gray Heppner, V Ann Stewart, Hitoshi Hasegawa, Sornchai Looareesuwan, G Dennis Shanks, R Scott Miller
Affiliations
- PMID: 15067072
- DOI: 10.4049/jimmunol.172.8.4926
Malaria blood stage parasites activate human plasmacytoid dendritic cells and murine dendritic cells through a Toll-like receptor 9-dependent pathway
Sathit Pichyangkul et al. J Immunol. 2004.
Abstract
A common feature of severe Plasmodium falciparum infection is the increased systemic release of proinflammatory cytokines that contributes to the pathogenesis of malaria. Using human blood, we found that blood stage schizonts or soluble schizont extracts activated plasmacytoid dendritic cells (PDCs) to up-regulate CD86 expression and produce IFN-alpha. IFN-alpha production was also detected in malaria-infected patients, but the levels of circulating PDCs were markedly reduced, possibly because of schizont-stimulated up-regulation of CCR7, which is critical for PDC migration. The schizont-stimulated PDCs elicited a poor T cell response, but promoted gamma delta T cell proliferation and IFN-gamma production. The schizont immune stimulatory effects could be reproduced using murine DCs and required the Toll-like receptor 9 (TLR9)-MyD88 signaling pathway. Although the only known TLR9 ligand is CpG motifs in pathogen DNA, the activity of the soluble schizont extract was far greater than that of schizont DNA, and it was heat labile and precipitable with ammonium sulfate, unlike the activity of bacterial DNA. These results demonstrate that schizont extracts contain a novel and previously unknown ligand for TLR9 and suggest that the stimulatory effects of this ligand on PDCs may play a key role in immunoregulation and immunopathogenesis of human falciparum malaria.
Similar articles
- The roles of Toll-like receptor 9, MyD88, and DNA-dependent protein kinase catalytic subunit in the effects of two distinct CpG DNAs on dendritic cell subsets.
Hemmi H, Kaisho T, Takeda K, Akira S. Hemmi H, et al. J Immunol. 2003 Mar 15;170(6):3059-64. doi: 10.4049/jimmunol.170.6.3059. J Immunol. 2003. PMID: 12626561 - Intracellular bacterial infection-induced IFN-gamma is critically but not solely dependent on Toll-like receptor 4-myeloid differentiation factor 88-IFN-alpha beta-STAT1 signaling.
Rothfuchs AG, Trumstedt C, Wigzell H, Rottenberg ME. Rothfuchs AG, et al. J Immunol. 2004 May 15;172(10):6345-53. doi: 10.4049/jimmunol.172.10.6345. J Immunol. 2004. PMID: 15128825 - Protein-DNA complex is the exclusive malaria parasite component that activates dendritic cells and triggers innate immune responses.
Wu X, Gowda NM, Kumar S, Gowda DC. Wu X, et al. J Immunol. 2010 Apr 15;184(8):4338-48. doi: 10.4049/jimmunol.0903824. Epub 2010 Mar 15. J Immunol. 2010. PMID: 20231693 Free PMC article. - Dendritic-cell function in Toll-like receptor- and MyD88-knockout mice.
Kaisho T, Akira S. Kaisho T, et al. Trends Immunol. 2001 Feb;22(2):78-83. doi: 10.1016/s1471-4906(00)01811-1. Trends Immunol. 2001. PMID: 11286707 Review. - The immunobiology of the TLR9 subfamily.
Wagner H. Wagner H. Trends Immunol. 2004 Jul;25(7):381-6. doi: 10.1016/j.it.2004.04.011. Trends Immunol. 2004. PMID: 15207506 Review. No abstract available.
Cited by
- Apoptosis and dysfunction of blood dendritic cells in patients with falciparum and vivax malaria.
Pinzon-Charry A, Woodberry T, Kienzle V, McPhun V, Minigo G, Lampah DA, Kenangalem E, Engwerda C, López JA, Anstey NM, Good MF. Pinzon-Charry A, et al. J Exp Med. 2013 Jul 29;210(8):1635-46. doi: 10.1084/jem.20121972. Epub 2013 Jul 8. J Exp Med. 2013. PMID: 23835848 Free PMC article. - CD36 modulates proinflammatory cytokine responses to Plasmodium falciparum glycosylphosphatidylinositols and merozoites by dendritic cells.
Kumar S, Gowda NM, Wu X, Gowda RN, Gowda DC. Kumar S, et al. Parasite Immunol. 2012 Jul;34(7):372-82. doi: 10.1111/j.1365-3024.2012.01367.x. Parasite Immunol. 2012. PMID: 22486596 Free PMC article. - Polymorphisms in the Fc gamma receptor IIIA and Toll-like receptor 9 are associated with protection against severe malarial anemia and changes in circulating gamma interferon levels.
Munde EO, Okeyo WA, Anyona SB, Raballah E, Konah S, Okumu W, Ogonda L, Vulule J, Ouma C. Munde EO, et al. Infect Immun. 2012 Dec;80(12):4435-43. doi: 10.1128/IAI.00945-12. Epub 2012 Oct 8. Infect Immun. 2012. PMID: 23045477 Free PMC article. - Malarial pigment hemozoin and the innate inflammatory response.
Olivier M, Van Den Ham K, Shio MT, Kassa FA, Fougeray S. Olivier M, et al. Front Immunol. 2014 Feb 5;5:25. doi: 10.3389/fimmu.2014.00025. eCollection 2014. Front Immunol. 2014. PMID: 24550911 Free PMC article. Review. - What really happens to dendritic cells during malaria?
Wykes MN, Good MF. Wykes MN, et al. Nat Rev Microbiol. 2008 Nov;6(11):864-70. doi: 10.1038/nrmicro1988. Epub 2008 Aug 19. Nat Rev Microbiol. 2008. PMID: 18711429 Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources