Brain microvessel cross-presentation is a hallmark of experimental cerebral malaria

Shanshan W. Howland, Chek Meng Poh, Sin Yee Gun, Carla Claser, Benoit Malleret, Nilabh Shastri, Florent Ginhoux, Gijsbert M. Grotenbreg, Laurent Rénia

Research output: Contribution to journalArticle

Abstract

Cerebral malaria is a devastating complication of Plasmodium falciparum infection. Its pathogenesis is complex, involving both parasite- and immune-mediated events. CD8+ T cells play an effector role in murine experimental cerebral malaria (ECM) induced by Plasmodium berghei ANKA (PbA) infection. We have identified a highly immunogenic CD8 epitope in glideosome-associated protein 50 that is conserved across rodent malaria species. Epitope-specific CD8+ T cells are induced during PbA infection, migrating to the brain just before neurological signs manifest. They are functional, cytotoxic and can damage the blood-brain barrier in vivo. Such CD8+ T cells are also found in the brain during infection with parasite strains/species that do not induce neuropathology. We demonstrate here that PbA infection causes brain microvessels to cross-present parasite antigen, while non-ECM-causing parasites do not. Further, treatment with fast-acting anti-malarial drugs before the onset of ECM reduces parasite load and thus antigen presentation in the brain, preventing ECM death. Thus our data suggest that combined therapies targeting both the parasite and host antigen-presenting cells may improve the outcome of CM patients. Cerebral malaria (CM) remains a deadly yet poorly understood complication of Plasmodium falciparum infection. Here, brain microvessels cross-present P. berghei epitopes that elicit a strong CD8-response resulting in experimental CM pathogenesis.

Original languageEnglish (US)
Pages (from-to)916-931
Number of pages16
JournalEMBO Molecular Medicine
Volume5
Issue number7
DOIs
StatePublished - Jul 1 2013
Externally publishedYes

Fingerprint

Cross-Priming
Cerebral Malaria
Microvessels
Plasmodium berghei
Brain
Parasites
Malaria
Epitopes
Plasmodium falciparum
T-Lymphocytes
Infection
Parasite Load
Parasitic Diseases
Antigen Presentation
Antimalarials
Antigen-Presenting Cells
Blood-Brain Barrier
Rodentia
Antigens

Keywords

  • Brain
  • Cross-presentation
  • Malaria
  • Pathology
  • T cells

ASJC Scopus subject areas

  • Molecular Medicine

Cite this

Howland, S. W., Poh, C. M., Gun, S. Y., Claser, C., Malleret, B., Shastri, N., ... Rénia, L. (2013). Brain microvessel cross-presentation is a hallmark of experimental cerebral malaria. EMBO Molecular Medicine, 5(7), 916-931. https://doi.org/10.1002/emmm.201202273

Brain microvessel cross-presentation is a hallmark of experimental cerebral malaria. / Howland, Shanshan W.; Poh, Chek Meng; Gun, Sin Yee; Claser, Carla; Malleret, Benoit; Shastri, Nilabh; Ginhoux, Florent; Grotenbreg, Gijsbert M.; Rénia, Laurent.

In: EMBO Molecular Medicine, Vol. 5, No. 7, 01.07.2013, p. 916-931.

Research output: Contribution to journalArticle

Howland, SW, Poh, CM, Gun, SY, Claser, C, Malleret, B, Shastri, N, Ginhoux, F, Grotenbreg, GM & Rénia, L 2013, 'Brain microvessel cross-presentation is a hallmark of experimental cerebral malaria', EMBO Molecular Medicine, vol. 5, no. 7, pp. 916-931. https://doi.org/10.1002/emmm.201202273
Howland, Shanshan W. ; Poh, Chek Meng ; Gun, Sin Yee ; Claser, Carla ; Malleret, Benoit ; Shastri, Nilabh ; Ginhoux, Florent ; Grotenbreg, Gijsbert M. ; Rénia, Laurent. / Brain microvessel cross-presentation is a hallmark of experimental cerebral malaria. In: EMBO Molecular Medicine. 2013 ; Vol. 5, No. 7. pp. 916-931.
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