Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Sep 10:9:2016.
doi: 10.3389/fimmu.2018.02016. eCollection 2018.

Cerebral Malaria in Mouse and Man

Nazanin Ghazanfari  1   2 , Scott N Mueller  1   2 , William R Heath  1   2
Affiliations
Review

Cerebral Malaria in Mouse and Man

Nazanin Ghazanfari et al. Front Immunol. .

Abstract

Cerebral malaria (CM) is an acute encephalopathy caused by the malaria parasite Plasmodium falciparum, which develops in a small minority of infected patients and is responsible for the majority of deaths in African children. Despite decades of research on CM, the pathogenic mechanisms are still relatively poorly defined. Nevertheless, many studies in recent years, using a combination of animal models, in vitro cell culture work, and human patients, provide significant insight into the pathologic mechanisms leading to CM. In this review, we summarize recent findings from mouse models and human studies on the pathogenesis of CM, understanding of which may enable development of novel therapeutic approaches.

Keywords: Plasmodium berghei; Plasmodium falciparum; T cells; blood-brain barrier; cerebral malaria.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Immunopathology of ECM. In response to Plasmodium blood-stage infection, pro-inflammatory cytokines such as IFN-γ and TNF are produced by various immune cells. (1) These cytokines promote the up-regulation of adhesion molecules on brain endothelial cells. iRBCs sequester in the cerebral microvasculature and bind to receptors on the endothelial cells such as ICAM-1. (2) IFN-γ induces the expression of CXCL10 by brain endothelial cells. IFN-γ-induced CXCL10 enhances the adhesion of T cells to cerebrovascular endothelium and prevents their detachment from the brain vasculature. (3) Parasite antigens can be transferred from the iRBC into the endothelial cell. This interaction leads to opening of the intercellular tight junctions. Brain endothelial cells can phagocytize parasite antigens and cross-present them to CD8+ T lymphocytes. (4) iRBC can also directly activate platelets and stimulate the release of CXCL4 early in the course of ECM. CXCL4 induces the production of TNF by T cells and macrophages, which then causes more platelets to adhere to the endothelium. Enhanced expression of CXCR3-binding chemokines such as CXCL9, CXCL10, and CXCL4 in the brains of PbA-infected mice induces T cell migration to the brain in the late stage of ECM. (5) Accumulation of iRBCs and immune cells in cerebral vessels leads to vascular obstruction, increased pressure within the brain blood vessels, and increased permeability of the BBB, facilitating edema, and brain swelling.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. WHO . World Malaria Report 2017. Geneva: World Health Organization; (2017).
    1. WHO World Malaria Report. 2015. Geneva: World Health Organization; (2015).
    1. Crompton PD, Moebius J, Portugal S, Waisberg M, Hart G, Garver LS, et al. . Malaria immunity in man and mosquito: insights into unsolved mysteries of a deadly infectious disease. Annu Rev Immunol. (2014) 32:157–87. 10.1146/annurev-immunol-032713-120220 - DOI - PMC - PubMed
    1. Coatney GR, National Institute of Allergy and Infectious Diseases (U.S.) The Primate Malarias. Bethesda, MD: U.S. National Institute of Allergy and Infectious Diseases; for sale by the Supt. of Docs., U.S. Govt. Print. Off., Washington; (1971). p. 366.
    1. White NJ, Pukrittayakamee S, Hien TT, Faiz MA, Mokuolu OA, Dondorp AM. Malaria. Lancet (2014) 383:723–35. 10.1016/B978-0-7020-5101-2.00044-3 - DOI - PubMed