Comparison of CD8+ T Cell Accumulation in the Brain During Human and Murine Cerebral Malaria.

Valentina Barrera,Michael J Haley,Patrick Strangward,Steve Kamiza,Danny A Milner,Alister G Craig,Elizabeth Attree,Karl B Seydel,Terrie E Taylor,Kevin N Couper

doi:10.3389/fimmu.2019.01747

Abstract

CD8+ T cells have been shown to play a critical role in the pathogenesis of experimental cerebral malaria (ECM) in mice, but their role in development of human cerebral malaria (HCM) remains unclear. Thus, in this study we have provided the first direct contrast of the accumulation of CD8+ T cells in the brain during HCM and ECM. HCM cases were from children who died of Plasmodium falciparum cerebral malaria at Queen Elizabeth Central Hospital (Malawi) between 2003 and 2010. ECM was induced by infecting C57BL/6J mice with P. berghei ANKA. We demonstrate similarities in the intracerebral CD8+ T cell responses in ECM and HCM, in particular an apparent shared choroid plexus—meningeal route of CD8+ T cell accumulation in the brain. Nevertheless, we also reveal some potentially important differences in compartmentalization of CD8+ T cells within the cerebrovascular bed in HCM and ECM.

Highlights

Cerebral malaria (HCM) is a severe neurological complication of Plasmodium falciparum (Pf ) infection that despite anti-malarial drug treatment often results in death or disability [1,2,3,4]
The increased density of CD8+ T cells in experimental cerebral malaria (ECM) compared with human cerebral malaria (HCM) was, not because CD8+ T cells were associated with a higher percentage of vessels, but was because there was a greater frequency of packed vessels with clusters of CD8+ T cells in ECM
There was no significant difference in the percentage of parasitized red blood cells (pRBCs) positive and pRBC negative vessels associated with CD8+ T cells during HCM, indicating that pRBC presence does not promote or impede CD8+ T cell accumulation during HCM (Figure 1Aiv)

Summary

Introduction

Cerebral malaria (HCM) is a severe neurological complication of Plasmodium falciparum (Pf ) infection that despite anti-malarial drug treatment often results in death or disability [1,2,3,4]. The pathological processes downstream of pRBC sequestration that drive resultant neuropathology remain unclear [7]. The P. berghei ANKA (Pb ANKA) murine model of experimental cerebral malaria (ECM) model has been extensively utilized to study the pathogenesis of HCM. In this model, intracerebral CD8+ T cells play a major role in disruption of the blood brain barrier and formation of cerebral pathology [8, 9]. Whether CD8+ T cells contribute to the development of HCM is unknown and has remained a matter of significant debate in the malaria community [10]

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Results

Conclusion