Skip to content

Research at St Andrews

Babesia divergens glycosylphosphatidylinositols modulate blood coagulation and induce Th2-biased cytokine profiles in antigen presenting cells

Research output: Contribution to journalArticle


Françoise Debierre-Grockiego, Terry K. Smith, Stéphane Delbecq, Céline Ducournau, Louis Lantier, Jörg Schmidt, Virginie Brès, Isabelle Dimier-Poisson, Ralph T. Schwarz, Emmanuel Cornillot

School/Research organisations


Glycosylphosphatidylinositols (GPIs) are glycolipids described as toxins of protozoan parasites due to their inflammatory properties in mammalian hosts characterized by the production of interleukin (IL)-1, IL-12 and tumor necrosis factor (TNF)-α. In the present work, we studied the cytokines produced by antigen presenting cells in response to ten different GPI species extracted from Babesia divergens, responsible for babesiosis. Interestingly, B. divergens GPIs induced the production of anti-inflammatory cytokines (IL-2, IL-5) and of the regulatory cytokine IL-10 by macrophages and dendritic cells. In contrast to all protozoan GPIs studied until now, GPIs from B. divergens did not stimulate the production of TNF-α and IL-12, leading to a unique Th1/Th2 profile. Analysis of the carbohydrate composition of the B. divergens GPIs indicated that the di-mannose structure was different from the evolutionary conserved tri-mannose structure, which might explain the particular cytokine profile they induce. Expression of major histocompatibility complex (MHC) molecules on dendritic cells and apoptosis of mouse peritoneal cells were also analysed. B. divergens GPIs did not change expression of MHC class I, but decreased expression of MHC class II at the cell surface, while GPIs slightly increased the percentages of apoptotic cells. During pathogenesis of babesiosis, the inflammation-coagulation auto-amplification loop can lead to thrombosis and the effect of GPIs on coagulation parameters was investigated. Incubation of B. divergens GPIs with rat plasma ex vivo led to increase of fibrinogen levels and to prolonged activated partial thromboplastin time, suggesting a direct modulation of the extrinsic coagulation pathway by GPIs.


Original languageEnglish
Pages (from-to)135-144
Number of pages10
Early online date1 Oct 2019
Publication statusPublished - Dec 2019

    Research areas

  • Antigen presentation, Coagulation, Glycosylphosphatidylinositol, Interleukin, Major histocompatibility complex

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. The importance of 1,5-oxygen···chalcogen interactions in enantioselective isochalcogenourea catalysis

    Young, C. M., Elmi, A., Pascoe, D. J., Morris, R. K., McLaughlin, C., Woods, A., Frost, A., De La Houpliere, A., Ling, K. B., Smith, T. K., Slawin, A. M. Z., Willoughby, P. H., Cockroft, S. L. & Smith, A. D., 13 Dec 2019, (Accepted/In press) In : Angewandte Chemie International Edition. In press

    Research output: Contribution to journalArticle

  2. Allosteric activation of an ion channel triggered by modification of mechanosensitive nano-pockets

    Kapsalis, C., Wang, B., El Mkami, H., Pitt, S. J., Schnell, J., Smith, T. K., Lippiat, J., Bode, B. E. & Pliotas, C., 10 Oct 2019, In : Nature Communications. 10, 14 p., 4619.

    Research output: Contribution to journalArticle

  3. Structure‐based design, synthesis and biological evaluation of bis‐tetrahydropyran furan acetogenin mimics targeting the trypanosomatid F1 component of ATP synthase

    Zacharova, M., Tulloch, L., Gould, E., Fraser, A., King, E., Menzies, S., Smith, T. K. & Florence, G. J., 1 Sep 2019, In : European Journal of Organic Chemistry. 2019, 31-32, p. 5434-5440 8 p.

    Research output: Contribution to journalArticle

  4. Plasma non-esterified fatty acids contribute to increased coagulability in type-2 diabetes through altered plasma zinc speciation

    Sobczak, A. I. S., Katundu, K. G. H., Phoenix, F. A., Khazaipoul, S., Yu, R., Lampiao, F., Stefanowicz, F., Blindauer, C. A., Pitt, S. J., Smith, T. K., Ajjan, R. A. & Stewart, A. J., 28 Aug 2019, In : biorxiv. 38 p.

    Research output: Contribution to journalArticle

  5. Novel benzothiazole-based ureas as 17β-HSD10 inhibitors, a potential Alzheimer’s disease treatment

    Aitken, L., Benek, O., McKelvie, B., Hughes, R. E., Hroch, L., Schmidt, M., Major, L. L., Vinklarova, L., Kuca, K., Smith, T. K., Musilek, K. & Gunn-Moore, F. J., 29 Jul 2019, In : Molecules. 24, 15, 2757.

    Research output: Contribution to journalArticle

Related by journal

  1. Plasma fatty acid levels may regulate the Zn2+-dependent activities of histidine-rich glycoprotein.

    Stewart, A. J., Blindauer, CA. & Sadler, PJ., 2009, In : Biochimie. 91, p. 1518-1522 5 p.

    Research output: Contribution to journalArticle

  2. Crystal structures of the bacterial ribosomal decoding site complexed with amikacin containing the gamma-amino-alpha-hydroxybutyrl (haba) group

    Kondo, J., Francois, B., Russell, R. J. M., Murray, JB. & Westhof, E., Aug 2006, In : Biochimie. 88, p. 1027-1031 5 p.

    Research output: Contribution to journalArticle

  3. Inhibitors of glycosyl-phosphatidylinositol anchor biosynthesis

    de Macedo, C. S., Shams-Eldin, H., Smith, T. K., Schwarz, R. T. & Azzouz, N., 2003, In : Biochimie. 85, 3-4, p. 465-472 8 p.

    Research output: Contribution to journalReview article

  4. The translational stop signal: Codon with a context, or extended factor recognition element?

    Tate, WP., Poole, ES., Dalphin, ME., Major, LL., Crawford, DJG. & Mannering, SA., 1996, In : Biochimie. 78, 11-12, p. 945-952 8 p.

    Research output: Contribution to journalArticle

ID: 262577344